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Abstract (english)


Hepatic encephalopathy (HE) is a neuropsychological syndrome which may accompany acute or chronic liver failure, being mainly due to the toxic effect of ammonia on the central nervous system [83]. HE encompasses a wide clinical spectrum, ranging from minimal forms, which are only detected by use of neuropsychological and/or electrophysiological techniques, to coma [7,8, 11, 144, 175, 190]. HE, even in its minimal form, impinges on quality of life and self-sufficiency [10, 76, 120, 164] and it carries negative prognostic value in terms of survival. Thus it is useful to identify patients with HE and reduced life expectancy, also for purposes of transplant selection procedures. The electrophysiological diagnosis of HE is based on the detection of slow wake-EEG frequencies [8]. However, some studies have shown that the regional distribution of the wake-EEG rhythms is also abnormal [126]. The detection of HE through psychometric and electrophysiological techniques is usually carried out in "standard" conditions. More recently, it has been proposed to artificially induce a condition of hyperammonaemia, thus simulating HE, by the oral administration of an amino-acid load (AAL). These amino-acids mimic the composition of hemoglobin, thus reproducing, at least to some extent, the HE which is observed after a gastrointestinal bleed [4, 65]. This allows doctors and researchers to measure more directly a patient's sensitivity to hyperammonaemia.
Disorders of the sleep-wake rhythm are common in patients with cirrhosis, heavily affecting their quality of life [129]. Sleep is regulated by the interaction of two processes: a homeostatic and a circadian process [31]. The former determines the propensity to fall asleep in connection to prior sleep-wake history (i.e. the need for sleep increases with prolonged wakefulness). The latter, which is reflected in the 24-hour rhythm of the hormone melatonin (high plasma levels at night and extremely low levels in the daytime), determines the alternation of periods of low/high sleep propensity in relation to environmental light/dark conditions. The interaction of such two processes results in a high likelihood of falling asleep after a prolonged period of wakefulness and when it gets dark, namely in the evening.
The alterations of the sleep-wake rhythm in patients with liver have traditionally been interpreted as being part of the HE syndrome [175]. More recent data suggest that this is the case for excessive daytime sleepiness, while insomnia probably has a different pathogenesis [128]. The causes of sleep-wake abnormalities in patients with cirrhosis are not completely clear. The documented changes in the circadian system (reduced sensitivity to light and altered rhythm/metabolism of melatonin) do not offer a complete explanation [128, 129]. Sleep can also be studied by polysomnography, which reflects homeostatic regulation. Information on homeostatic regulation in these patients is limited [179]. The exact neurochemical correlates of human sleep homeostasis remain unknown, although adenosinergic neurotransmission is likely to be implicated. In healthy subjects caffeine, an adenosine receptor antagonist, significantly affects both the wake EEG (reduction in theta activity, which increases with the increase of sleep pressure) and the sleep EEG, and attenuates the subjective sleepiness which is associated with prolonged wakefulness and sleep deprivation [106].

This set of studies was performed in order to evaluate:
- the effect of induced hyperammonaemia on neuropsychological performance and the wake EEG (Study 1);
- the relationship between daytime sleepiness, HE, and the sleep EEG (Study 2);
- the effects of ammonia-lowering drugs (L-ornithine-L-aspartate, LOLA) and caffeine on the wake and sleep EEG (Study3).

Materials and methods.
Well-characterized patients with compensated cirrhosis and with no history of HE and matched healthy volunteers were enrolled and underwent:
- Assessing and monitoring the quality and time of sleep with questionnaires and sleep diaries.
- Oral load of amino acids (AAL), mixture of 54 grams of amino acids mimicking the hemoglobin contained in 400 ml of blood, taken in the morning per os.
- Detection time of subjective sleepiness and capillary ammonia.
- Neuropsychological assessment, including psychometric paper and pencil (PHES battery), computerized psychometry and EEG recording of wakefulness.
- Polysomnographic recording. Patients were given the opportunity to sleep between 17:00 and 19:00 in favorable environmental conditions (dark and isolated room).
- Administration of LOLA 20g in 500cc of saline in 4-hour infusion (8-12) or 200mg caffeine per os(at 10 am) under inducedhyperammonemia (Study 3).

Study 1. Effects of hyperammonaemia on neuropsychological performance and waking EEG.
- The study population included 10 patients with liver cirrhosis (9 men, mean ± SD, age: 54 ± 14 years) and 10 healthy volunteers matched for age and sex (5 men, 49 ± 13 years). One patient (male 55 years) underwent EEG recording also after the insertion of a trans-jugular portal-systemic shunt (TIPS), a procedure which is associated with increased risk of HE.
- The subjects were studied with a neuropsychological evaluation and monitoring of capillary ammonia at baseline (4th or 8th day of the study) and after oral amino acids (AAL) (4th or 8th day of the study).
- At baseline, patients had higher ammonia levels than healthy volunteers [median (interquartile range): 30 (22-44) vs. 38 (34-47)mmol/L, p < 0.1]. The AAL has produced the expected increase in ammonia in both groups, the peak of ammonia was higher (ammonia 11:00, p < 0.03) and more prolonged in patients.
- The AAL has produced a significant slowing of EEG waking such as to define the presence of a minimal HE in 2 (20 %) patients. By contrast, the AAL no significant changes in the psychometric performance paper & pencil or computerized.
- At baseline, the dominant frequency EEG activity was slower in patients compared to healthy volunteers in most derivations(p < 0.05). The AAL did not alter the dominant frequency in healthy volunteers, while that of patients slowed further along the midline (p < 0.05).
- At baseline, the waking EEG spectral power had an occipital-temporal predominance in both groups. The patients had higher power in all derivations (p < 0.05). The AAL induced a significant increase of power in almost all derivations in healthy volunteers (p < 0.05), while it did not affect power in patients.
- In the patient studied on three occasions, the spectral power of dominant wake EEG progressively increased from baseline after AAL and after TIPS, while there was a decrease in the frequency of the wake EEG after insertion of TIPS.

Study 2. Effect of hyperammonaemia on sleepiness and sleep EEG.
- The study population (see Study 1) was subjected to neuropsychological assessment, detection time of sleepiness and ammonia and polysomnographic recording, in basal conditions (4th or 8th day of the study) and after AAL (4th or 8th day of the study).
The AAL has produced
- an increase in subjective sleepiness parallel to increased concentrations of ammonia both in patients and in healthy volunteers;in both groups, the peak of sleepiness (at 11 am), absent in basal condition, coincides with the peak concentration of ammonia (p <0.01);
- an increase in sleep duration in healthy volunteers compared with baseline (mean ± SD, 49.3 ± 26.6vs. 30.4 ± 15.6 min), although the differences are not statistically significant (p 0.08). No changes arebeen observedon the duration of sleep in patients;
- significant decrease in the relative power beta (fast activity)of the sleep EEG in healthy volunteers (p < 0.05);
- significant reduction in the relative power of delta (activity very slow)of thesleep EEG in patients (p < 0.05).

Study 3. Effects of L-ornithine-L-aspartate (LOLA, substance that reduce ammonia) and caffeine (adenosine receptor antagonist) on cognitive performance,wake and sleep EEG in conditions of induced hyperammonaemia.
- The study population consisted of 6 patients with liver cirrhosis (5 men, mean ± SD, age: 61 ± 9 years) and 5 healthy volunteers matched for age, sex and level of education (4 men, 49 ± 12 years).
- The subjects were studied with neuropsychological assessment, detection sleepiness and ammonia hourly and polysomnographic recording, after AAL, AAL+LOLA, AAL+caffeine) on the 4th, 11th and 18th day of the study.
- patients presented a paper and pencil and computerized psychometric performance significantly worse than the healthy volunteers (p < 0.05);
- patients had levels of ammonia above those of healthy volunteers in all conditions;
the AAL has produced the expected increase of ammonia in both groups, with a peak higher and more prolonged in patients.
- The LOLA has resulted in a reduction although not significant levels of plasmatic ammonia in both groups.
- Neither the LOLA nor caffeine resulted in significant changes of subjective sleepiness, on psychometric performance and the wake EEG.
- Sleep EEG data are being analyzed (at the Institute of Pharmacology and Toxicology, University of Zurich, Switzerland).

- The waking EEG is extremely sensitive to hyperammonaemia.
- A moderate/chronic (patients in baseline) or acute (healthy volunteers after AAL) hyperammonaemia results in an increased power of the dominant EEG rhythm, especially over posterior and central areas of the scalp.
- An acute on chronic hyperammonaemia (patients after AAL) slows further the dominant EEG frequency.
- EEG parameters based on power can provide useful information to the neurophysiological definition of HE.
- Hyperammonaemia leads to a significant increase in subjective daytime sleepiness.
- Hyperammonaemia causes opposing changes in the sleep EEG of patients and controls, making the sleep of patients fragmented and more superficial, and that of healthy volunteers deeper and more stable.
- L-ornithine-L-aspartate leads to a reduction in the levels of ammonia.

Abstract (italian)

L'encefalopatia epatica (EE) è una sindrome neuropsichica che può accompagnare l'insufficienza epatica acuta o cronica ed è legata principalmente all'effetto tossico dell'ammonio sul sistema nervoso centrale [83]. Clinicamente, l'EE è caratterizzata da uno spettro di manifestazioni che va da forme minime, evidenziabili solo con tecniche psicometriche ed elettrofisiologiche, fino al coma, passando per quadri clinici di encefalopatia conclamata, caratterizzati da alterazioni neurologiche e psichiatriche più o meno invalidanti [7, 8, 11, 145, 176, 191]. L'EE, anche nelle sue forme minime, si ripercuote non solo sull'autonomia e sulla qualità di vita del paziente [10, 76, 121, 165], ma anche su quelle familiari e sulle strutture socio-sanitarie. Inoltre, contribuisce ad individuare pazienti con ridotta aspettativa di vita, per i quali può essere indicato l'inserimento in lista per trapianto di fegato. La diagnosi elettrofisiologica dell'EE si basa sulla rilevazione di un rallentamento delle frequenze dell'EEG [8]. Tuttavia, alcuni studi hanno dimostrato che anche la distribuzione regionale dei ritmi dell'EEG di veglia può essere anormale nei pazienti con cirrosi e soprattutto in quelli con EE [127]. Il rilievo di EE mediante tecniche psicometriche ed elettrofisiologiche viene di solito effettuato in condizioni basali. Più di recente, È stato proposto di indurre un’iperammoniemia e quindi di simulare una condizione di EE minima/conclamata lieve tramite la somministrazione orale di un carico di aminoacidi (COAA) mimanti l’emoglobina (simulazione di encefalopatia/iperammoniemia associate al sanguinamento digestivo) e di studiarne l’effetto su psicometria ed elettroencefalogramma [4, 65], misurando quindi più direttamente la sensibilità del singolo paziente all’iperammoniemia.
I disturbi del ritmo sonno-veglia sono comuni nei pazienti con cirrosi epatica e incidono pesantemente sulla loro qualità di vita [130]. Il sonno è regolato dall'interazione tra due processi: un processo omeostatico e uno circadiano [31]. Il primo determina la propensione ad addormentarsi in rapporto alla precedente storia di sonno/veglia, facendo sì che la necessità di dormire aumenti con il prolungarsi della veglia. Invece il processo circadiano, che si riflette nel ritmo 24-ore dell'ormone melatonina (livelli plasmatici elevati la notte e pressoché assenti di giorno), determina l'alternarsi di periodi di bassa/alta propensione all’addormentamento in relazione ai segnali ambientali di luce/buio. Il risultato dell’interazione fra questi due processi fa sì che la probabilità di addormentarsi sia alta quando sono passate numerose ore dal risveglio e quando si fa buio, vale a dire la sera.
Le alterazioni del ritmo sonno-veglia dei pazienti con cirrosi epatica sono state tradizionalmente interpretate come facenti parte del complesso sindromico dell’encefalopatia epatica [176]. Dati più recenti suggeriscono che l'eccessiva sonnolenza diurna sia effettivamente un tratto dell'EE, mentre l'insonnia abbia una patogenesi distinta [129]. Tuttavia le cause di questi disturbi restano dibattute. Le documentate alterazioni del sistema di regolazione circadiano (ridotta sensibilità alla luce e disturbato ritmo/metabolismo della melatonina) non offrono una spiegazione esauriente [129, 130]. Anche le informazioni disponibili in questi pazienti sulla regolazione omeostatica del sonno, che può essere studiata con la polisonnografia, sono scarse [180]. Le esatte correlazioni neurochimiche dell’omeostasi del sonno umano rimangono sconosciute, anche se sempre più numerose evidenze dimostrano un possibile importante ruolo nella trasmissione adenosinergica. Nei soggetti sani infatti la caffeina, un antagonista recettoriale dell'adenosina, influenza in modo significativo l’elettroencefalogramma di veglia (riduzione dell'attività theta, che aumenta con l’aumentare della pressione del sonno) e di sonno, e attenua la sonnolenza soggettiva associata alla veglia prolungata/deprivazione di sonno [107].

I miei studi di dottorato sono stati eseguiti allo scopo di valutare, in un gruppo di pazienti con la cirrosi epatica e in un gruppo di volontari sani, l’effetto dell’iperammonimia indotta:
- sulla prestazione neuropsichica e sull'EEG di veglia (Studio 1);
- sul rapporto tra sonnolenza diurna ed EE e sulle caratteristiche dell'EEG di sonno (Studio 2);
- sugli effetti di sostanze ipoammoniemizzanti (L-ornitina-L-aspartato, LOLA) e della caffeina (antagonista del recettore dell'adenosina) su EEG di veglia e su EEG di sonno (Studio 3).

Materiali e metodi.
Sono stati arruolati pazienti ben caratterizzati con cirrosi epatica compensata e con anamnesi negativa per EE minima o conclamata e volontari sani confrontabili per età , sesso e livello d'istruzione.
I soggetti sono stati sottoposti a:
- valutazione e monitoraggio della qualità e degli orari del sonno con questionari e diari del sonno;
- carico orale di aminoacidi (COAA), miscela di 54 gr di aminoacidi mimanti l’emoglobina contenuta in 400 ml di sangue, assunta al mattino per os;
- rilevazione oraria di sonnolenza soggettiva ed ammoniemia capillare;
- valutazione neuropsichica, comprendente psicometria carta e matita (batteria PHES), psicometria computerizzata e registrazione dell’EEG di veglia.
- registrazione polisonnografica. Ai pazienti veniva data la possibilità di dormire tra le 17:00 e le 19:00 in condizioni ambientali favorevoli (stanza buia ed isolata).
- somministrazione di LOLA 20gr in 500cc di soluzione fisiologica in infusione di 4 ore (8-12) o caffeina 200mg per os (ore 10) in corso di iperammoniemia dopo COAA (studio 3).

Studio 1. Effetti dell’iperammoniemia sulla prestazione neuropsichica e sull’EEG di veglia
• la popolazione di studio comprendeva 10 pazienti con cirrosi epatica (9 uomini; media ± SD; età : 54 ± 14 anni) e 10 volontari sani appaiati per età e sesso (5 uomini, 49 ± 13 anni). Un paziente (maschio di 55 anni) è stato sottoposto a registrazione EEG anche dopo l'inserimento di uno shunt porto-sistemico trans-giugulare (TIPS), procedura associata ad un aumentato rischio di sviluppo di EE.
• I soggetti sono stati studiati con una valutazione neuropsichica e monitoraggio dell’ammoniemia oraria in condizioni basali (4° o 8° giorno di studio) e dopo carico orale di aminoacidi (COAA) (4° o 8° giorno di studio).
• Al basale, i pazienti avevano livelli di ammoniaca superiori a quelli dei volontari sani [mediana (range interquartile): 30 (22-44) vs 38 (34-47) µmol/L, p < 0.1]. Il COAA ha prodotto l’atteso aumento dell’ammoniemia in entrambi i gruppi; il picco dell’ammoniemia è stato più alto (ammoniemia ore 11:00, p<0.03) e più prolungato nei pazienti.
• Il COAA ha prodotto un rallentamento significativo dell’EEG di veglia tale da definire la presenza di EE minima in 2 (20%) pazienti. Per contro, il COAA non ha prodotto cambiamenti significativi della prestazione psicometrica carta&matita o computerizzata.
• Al basale, la frequenza dominante dell'attività EEG era più lenta nei pazienti rispetto ai volontari sani in diverse derivazioni (p<0.05). Il COAA non ha alterato la frequenza dominante nei volontari sani, mentre ha rallentato ulteriormente quella dei pazienti lungo la linea mediana (p<0.05)
• In condizioni basali, la potenza spettrale dell’EEG di veglia aveva una predominanza occipito-temporale in entrambi i gruppi. I pazienti avevano potenza superiore in tutte le derivazioni (p<0.05). Il COAA ha indotto un aumento significativo di potenza in quasi tutte le derivazioni nei volontari sani (p<0.05), mentre nessuna modifica della potenza è stata osservata nei pazienti.
• Nel paziente studiato in tre occasioni, la potenza dell'attività dominante dell’EEG è aumentata progressivamente dal basale, dopo COAA, dopo TIPS, mentre si è osservato un calo della frequenza dominante dell’EEG dopo l’inserimento della TIPS.

Studio 2. Effetto dell’iperammoniemia su sonnolenza ed EEG di sonno
• la popolazione di studio (vedi studio 1) è stata sottoposta a valutazione neuropsichica, rilevazione oraria di sonnolenza ed ammoniemia oraria e registrazione polisonnografica, in condizioni basali (4° o 8° giorno di studio) e dopo COAA (4° o 8° giorno di studio).
Il COAA ha prodotto
• un aumento della sonnolenza soggettiva parallela all’aumento delle concentrazioni dell’ammoniaca sia nei pazienti che nei volontari sani; in entrambi i gruppi il picco di sonnolenza (ore 11), assente in condizione basale, coincide con il picco di concentrazione dell’ammoniaca (p<0.01)
• un aumento della durata del sonno nei volontari sani rispetto al basale (media ± SD, 49.3 ± 26.6 vs 30.4 ± 15.6 min), sebbene le differenze non siano statisticamente significative (p= 0.08). Nessuna modifica sulla durata del sonno nei pazienti.
• diminuzione significativa della potenza relativa beta (attività veloce) dell’EEG di sonno nei volontari sani (p<0.05);
• riduzione significativa della potenza relativa delta (attività molto lenta) del sonno in pazienti (p<0.05);

Studio 3. Effetti di L-ornitina-L-aspartato (LOLA, sostanza ipoammoniemizzante) e di caffeina (antagonista del recettore dell’adenosina) su prestazione cognitiva, EEG di veglia e sonno in condizioni di iperammoniemia indotta
• la popolazione di studio comprendeva 6 pazienti con cirrosi epatica (5 uomini; media ± SD; età : 61 ± 9 anni) e 5 volontari sani appaiati per età , sesso e livello d’istruzione (4 uomini, 49 ± 12 anni).
• I soggetti sono stati studiati con valutazione neuropsichica, rilevazione oraria di sonnolenza ed ammoniemia oraria e registrazione polisonnografica, dopo COAA COAA+LOLA- COAA + caffeina) il 4°, 11° e 18° giorno di studio.
• I pazienti rispetto ai volontari sani hanno presentato una prestazione psicometrica sia carta e matita che computerizzata significativamente peggiore rispetto ai volontari sani (p<0.05)
• i pazienti avevano livelli di ammoniaca superiori a quelli dei volontari sani in tutte le condizioni; il COAA ha prodotto l’atteso aumento dell’ammoniemia in entrambi i gruppi, con un picco più elevato e più prolungato nei pazienti.
• il LOLA ha determinato una riduzione seppur non significativa dei livelli plasmatici dell’ammonio in entrambi i gruppi
• né il LOLA né la caffeina hanno determinato cambiamenti significativi su la sonnolenza soggettiva, su prestazione psicometrica e su EEG di veglia
• i dati sull’EEG di sonno sono in corso di analisi (presso l’Istituto Farmacologia e Tossicologia dell’Università di Zurigo, Svizzera).

- l'EEG di veglia è estremamente sensibile all'iperammoniemia
- un’iperammoniemia moderata/cronica (pazienti in basale) o acuta (volontari sani dopo COAA) si traduce in una maggiore potenza del ritmo dominante di EEG, specialmente sulle zone posteriori dello scalpo.
- un’iperammoniemia acuta su cronica (pazienti dopo COAA) rallenta ulteriormente la frequenza dominante dell'EEG
- parametri EEG basati sulla potenza possono fornire informazioni utili alla definizione neurofisiologica dell'EE.
- l’iperammoniemia comporta un notevole aumento della sonnolenza diurna soggettiva
- l’iperammoniemia provoca cambiamenti opposti nell’EEG di sonno dei pazienti e dei controlli, rendendo il sonno dei pazienti più superficiale ed interrotto e quello dei volontari sani più profondo e stabile.
- l’EE può forse quindi essere inquadrata come un difetto di vigilanza, che rende simili l’EEG di sonno a quello di veglia, compromettendo quindi il raggiungimento di una veglia “piena” e la produzione di un sonno “ristoratore”.
- L-ornitina-L-aspartato determina una riduzione dei livelli di ammoniemia

Statistiche Download - Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Amodio, Piero and Montagnese, Sara
Data di deposito della tesi:26 January 2014
Anno di Pubblicazione:26 January 2014
Key Words:encefalopatia epatica/ hepatic encephalopathy
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/09 Medicina interna
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:6383
Depositato il:20 Sep 2016 14:32
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8. BIBLIOGRAFIA Cerca con Google

1. Achermann, P., A.A. Borbely, Sleep homeostasis and models of sleep regulation. In: Kryger MH, ed. Principles and Practice of Sleep Medicine. 5th ed. Philadelphia: Elsevier Saunders, 2010. Cerca con Google

2. Ahboucha, S., R.F. Butterworth, The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem Int, 2008. 52(4-5): p. 575-87. Cerca con Google

3. Akerstedt, T., M. Gillberg, Subjective and objective sleepiness in the active individual. Int J Neurosci, 1990. 52(1-2): p. 29-37. Cerca con Google

4. Al Mardini, H., A. Douglass, C. Record, Amino acid challenge in patients with cirrhosis and control subjects: ammonia, plasma amino acid and EEG changes. Metab Brain Dis, 2006. 21(1): p. 1-10. Cerca con Google

5. Als-Nielsen, B., R.L. Koretz, L.L. Kjaergard, C. Gluud, Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev, 2003(2): p. CD001939. Cerca con Google

6. Amodio, P., C. Bemeur, R. Butterworth, J. Cordoba, et al., The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology, 2013. 58(1): p. 325-36. Cerca con Google

7. Amodio, P., F. Campagna, S. Olianas, P. Iannizzi, et al., Detection of minimal hepatic encephalopathy: normalization and optimization of the Psychometric Hepatic Encephalopathy Score. A neuropsychological and quantified EEG study. J Hepatol, 2008. 49(3): p. 346-53. Cerca con Google

8. Amodio, P., P. Marchetti, F. Del Piccolo, M. de Tourtchaninoff, et al., Spectral versus visual EEG analysis in mild hepatic encephalopathy. Clin Neurophysiol, 1999. 110(8): p. 1334-1344. Cerca con Google

9. Amodio, P., P. Marchetti, F. Del Piccolo, C. Rizzo, et al., Study on the Sternberg paradigm in cirrhotic patients without overt hepatic encephalopathy. Metab Brain Dis, 1998. 13(2): p. 159-72. Cerca con Google

10. Amodio, P., A. Pellegrini, P. Amista, S. Luise, et al., Neuropsychological-neurophysiological alterations and brain atrophy in cirrhotic patients. Metab Brain Dis., 2003. 18(1): p. 63-78. Cerca con Google

11. Amodio, P., J.C. Quero, F. Del Piccolo, A. Gatta, et al., Diagnostic tools for the detection of subclinical hepatic encephalopathy: comparison of standard and computerized psychometric tests with spectral-EEG. Metab Brain Dis., 1996. 11(4): p. 315-327. Cerca con Google

12. Amodio, P., S. Schiff, F. Del Piccolo, D. Mapelli, et al., Attention dysfunction in cirrhotic patients: an inquiry on the role of executive control, attention orienting and focusing. Metab Brain Dis., 2005. 20(2): p. 115-127. Cerca con Google

13. Angeli, P., F. Wong, H. Watson, P. Gines, Hyponatremia in cirrhosis: Results of a patient population survey. Hepatology, 2006. 44(6): p. 1535-42. Cerca con Google

14. Apolone, G., P. Mosconi, The Italian SF-36 Health Survey: translation, validation and norming. J Clin Epidemiol, 1998. 51(11): p. 1025-36. Cerca con Google

15. Arendt, J., Light-dark control of melatonin synthesis. In: Melatonin and the Mammalian Pineal Gland. 1st ed. London Chapman & Hall, 1995: p. 66-109. Cerca con Google

16. Arendt, J., C. Bojkowski, C. Franey, J. Wright, et al., Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab, 1985. 60(6): p. 1166-73. Cerca con Google

17. Arendt, J., B. Middleton, P. Williams, G. Francis, et al., Sleep and circadian phase in a ship's crew. J Biol Rhythms, 2006. 21(3): p. 214-21. Cerca con Google

18. Bajaj, J.S., J. Cordoba, K.D. Mullen, P. Amodio, et al., Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther, 2011. 33(7): p. 739-47. Cerca con Google

19. Bajaj, J.S., K. Saeian, C.M. Schubert, M. Hafeezullah, et al., Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology, 2009. 50(4): p. 1175-1183. Cerca con Google

20. Bajaj, J.S., C.M. Schubert, D.M. Heuman, J.B. Wade, et al., Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology, 2010. 138(7): p. 2332-40. Cerca con Google

21. Baldy-Moulinier, M., A. Besset, B. Clavet, H. Michel, Etude polygraphique nycthemerale des endormissements et des reveils au cors des encephalopathies hepatiques. Rev E E G Neurophysiol, 1981. 11: p. 123-132. Cerca con Google

22. Baraldi, M., R. Avallone, L. Corsi, I. Venturini, et al., Endogenous benzodiazepines. Therapie, 2000. 55(1): p. 143-6. Cerca con Google

23. Basile, A.S., The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy. Synapse, 1991. 7(2): p. 141-50. Cerca con Google

24. Basile, A.S., N.L. Ostrowski, S.H. Gammal, E.A. Jones, et al., The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand. Neuropsychopharmacology, 1990. 3(1): p. 61-71. Cerca con Google

25. Bergonzi, P., A. Bianco, S. Mazza, G. Mennuni, et al., Organizzazione del sonno notturno in pazienti con cirrosi epatica: modificazioni prima e dopo trattamento con l-dopa e lattulosio. Riv Neurol, 1975. 45: p. 118-123. Cerca con Google

26. Bessman, A.N., G.S. Mirick, Blood ammonia levels following the ingestion of casein and whole blood. J Clin Invest, 1958. 37(7): p. 990-8. Cerca con Google

27. Bianchi, G., G. Marchesini, F. Nicolino, R. Graziani, et al., Psychological status and depression in patients with liver cirrhosis. Dig Liver Dis, 2005. 37(8): p. 593-600. Cerca con Google

28. Blake, H., R.W. Gerard, Brain potentials during sleep. Am J Physiol, 1937. 119: p. 692-703. Cerca con Google

29. Blei, A.T., J. Cordoba, Subclinical encephalopathy. Dig Dis, 1996. 14 Suppl 1: p. 2-11. Cerca con Google

30. Blei, A.T., S. Olafsson, G. Therrien, R.F. Butterworth, Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. Hepatology, 1994. 19(6): p. 1437-1444. Cerca con Google

31. Borbely, A.A., A two process model of sleep regulation. Hum Neurobiol, 1982. 1(3): p. 195-204. Cerca con Google

32. Borbely, A.A., F. Baumann, D. Brandeis, I. Strauch, et al., Sleep deprivation: effect on sleep stages and EEG power density in man. Electroencephalogr Clin Neurophysiol, 1981. 51(5): p. 483-95. Cerca con Google

33. Born, J., S. Muth, H.L. Fehm, The significance of sleep onset and slow wave sleep for nocturnal release of growth hormone (GH) and cortisol. Psychoneuroendocrinology, 1988. 13(3): p. 233-43. Cerca con Google

34. Boy, C., P.T. Meyer, G. Kircheis, M.H. Holschbach, et al., Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis. Eur J Nucl Med Mol Imaging, 2008. 35(3): p. 589-97. Cerca con Google

35. Broughton, R., J. Hasan, Quantitative topographic electroencephalographic mapping during drowsiness and sleep onset. J Clin Neurophysiol, 1995. 12(4): p. 372-86. Cerca con Google

36. Burchi, R., I saggi della funzionalità epatica e la prova dell'ammoniemia spontanea e provocata con lo studio della insufficienza funzionale del fegato. Folia clin chim micr, 1927. 2: p. 5. Cerca con Google

37. Burra, P., M. Dam, F. Chierichetti, U. Tedeschi, et al., 18F-fluorodeoxyglucose positron emission tomography study of brain metabolism in cirrhosis: effect of liver transplantation. Transplant Proc, 1999. 31(1-2): p. 418-20. Cerca con Google

38. Burra, P., G. Pizzolato, F. Orlando, A. Rossato, et al., Single-photon emission computed tomography with 99mTC-hexamethylpropyleneamineoxide in cirrhotic patients before and after liver transplantation. Transplant Proc, 1994. 26(6): p. 3677-8. Cerca con Google

39. Butterworth, J., C.R. Gregory, L.R. Aronson, Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. Metab Brain Dis, 1997. 12(4): p. 299-306. Cerca con Google

40. Butterworth, R.F., The neurobiology of hepatic encephalopathy. Semin Liver Dis, 1996. 16(3): p. 235-244. Cerca con Google

41. Butterworth, R.F., Pathophysiology of hepatic encephalopathy: a new look at ammonia. Metab Brain Dis, 2002. 17(4): p. 221-227. Cerca con Google

42. Butterworth, R.F., Hepatic encephalopathy. Alcohol Res Health, 2003. 27(3): p. 240-246. Cerca con Google

43. Butterworth, R.F., Pathogenesis of hepatic encephalopathy: update on molecular mechanisms. Indian J Gastroenterol, 2003. 22 Suppl 2: p. S11-S16. Cerca con Google

44. Butterworth, R.F., Neuronal cell death in hepatic encephalopathy. Metab Brain Dis, 2007. 22(3-4): p. 309-320. Cerca con Google

45. Butterworth, R.F., L. Spahr, S. Fontaine, G.P. Layrargues, Manganese toxicity, dopaminergic dysfunction and hepatic encephalopathy. Metab Brain Dis, 1995. 10(4): p. 259-267. Cerca con Google

46. Buysse, D.J., C.F. Reynolds, 3rd, T.H. Monk, S.R. Berman, et al., The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res, 1989. 28(2): p. 193-213. Cerca con Google

47. Carpenedo, R., G. Mannaioni, F. Moroni, Oxindole, a sedative tryptophan metabolite, accumulates in blood and brain of rats with acute hepatic failure. J Neurochem, 1998. 70(5): p. 1998-2003. Cerca con Google

48. Catafau, A.M., J. Kulisevsky, L. Berna, J. Pujol, et al., Relationship between cerebral perfusion in frontal-limbic-basal ganglia circuits and neuropsychologic impairment in patients with subclinical hepatic encephalopathy. J Nucl Med, 2000. 41(3): p. 405-10. Cerca con Google

49. Chu, N.S., S.S. Yang, Y.F. Liaw, Evoked potentials in liver diseases. J Gastroenterol Hepatol, 1997. 12(9-10): p. S288-S293. Cerca con Google

50. Conn, H.O., Trailmaking and number-connection tests in the assessment of mental state in portal systemic encephalopathy. Am J Dig Dis, 1977. 22(6): p. 541-550. Cerca con Google

51. Conn, H.O., C.M. Leevy, Z.R. Vlahcevic, J.B. Rodgers, et al., Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology, 1977. 72(4 Pt 1): p. 573-583. Cerca con Google

52. Cordoba, J., J. Cabrera, L. Lataif, P. Penev, et al., High prevalence of sleep disturbance in cirrhosis. Hepatology, 1998. 27(2): p. 339-45. Cerca con Google

53. Cordoba, J., R. Garcia-Martinez, M. Simon-Talero, Hyponatremic and hepatic encephalopathies: similarities, differences and coexistence. Metab Brain Dis, 2010. 25(1): p. 73-80. Cerca con Google

54. Cordoba, J., F. Sanpedro, J. Alonso, A. Rovira, 1H magnetic resonance in the study of hepatic encephalopathy in humans. Metab Brain Dis, 2002. 17(4): p. 415-429. Cerca con Google

55. Czeisler, C.A., J.F. Duffy, T.L. Shanahan, E.N. Brown, et al., Stability, precision, and near-24-hour period of the human circadian pacemaker. Science, 1999. 284(5423): p. 2177-81. Cerca con Google

56. Czeisler, C.A., G.S. Richardson, R.M. Coleman, J.C. Zimmerman, et al., Chronotherapy: resetting the circadian clocks of patients with delayed sleep phase insomnia. Sleep, 1981. 4(1): p. 1-21. Cerca con Google

57. Dam, M., P. Burra, U. Tedeschi, A. Cagnin, et al., Regional cerebral blood flow changes in patients with cirrhosis assessed with 99mTc-HM-PAO single-photon emission computed tomography: effect of liver transplantation. J Hepatol, 1998. 29(1): p. 78-84. Cerca con Google

58. Davidson, E.A., W.H. Summerskill, Psychiatric aspects of liver disease. Postgrad Med J, 1956. 32(372): p. 487-494. Cerca con Google

59. De Gennaro, L., M. Ferrara, G. Curcio, R. Cristiani, Antero-posterior EEG changes during the wakefulness-sleep transition. Clin Neurophysiol, 2001. 112(10): p. 1901-11. Cerca con Google

60. De Rui, M., S. Gaiani, B. Middleton, D.J. Skene, et al., Bright times for patients with cirrhosis and delayed sleep habits: a case report on the beneficial effect of light therapy. Am J Gastroenterol, 2011. 106(11): p. 2048-9. Cerca con Google

61. De Rui, M., S. Schiff, D. Aprile, P. Angeli, et al., Excessive daytime sleepiness and hepatic encephalopathy: it is worth asking. Metab Brain Dis, 2013. 28(2): p. 245-8. Cerca con Google

62. Delcker, A., B. Turowski, U. Mihm, P. Raab, et al., Proton MR spectroscopy of neurometabolites in hepatic encephalopathy during L-ornithine-L-aspartate treatment--results of a pilot study. Metab Brain Dis, 2002. 17(2): p. 103-11. Cerca con Google

63. Delorme, A., S. Makeig, EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods, 2004. 134(1): p. 9-21. Cerca con Google

64. Deutz, N.E., P.L. Reijven, M.C. Bost, C.L. van Berlo, et al., Modification of the effects of blood on amino acid metabolism by intravenous isoleucine. Gastroenterology, 1991. 101(6): p. 1613-20. Cerca con Google

65. Douglass, A., H. Al Mardini, C. Record, Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy. J Hepatol, 2001. 34(5): p. 658-64. Cerca con Google

66. Dudley, G.A., R.S. Staron, T.F. Murray, F.C. Hagerman, et al., Muscle fiber composition and blood ammonia levels after intense exercise in humans. J Appl Physiol Respir Environ Exerc Physiol, 1983. 54(2): p. 582-6. Cerca con Google

67. Fan, P., J. Lavoie, N.L. Le, J.C. Szerb, et al., Neurochemical and electrophysiological studies on the inhibitory effect of ammonium ions on synaptic transmission in slices of rat hippocampus: evidence for a postsynaptic action. Neuroscience, 1990. 37(2): p. 327-334. Cerca con Google

68. Fehér, J., I. Làng, A. Gogl, Effect of ornithine-aspartate infusion on elevated serum ammonia concentration in cirrhotic patients-results of a randomized, double-blind multicentre trial. Med Sci Monit, 1997. 3: p. 669-673. Cerca con Google

69. Ferenci, P., A. Lockwood, K. Mullen, R. Tarter, et al., Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology, 2002. 35(3): p. 716-721. Cerca con Google

70. Foley, J.M., C.W. Watson, R.D. Adams, Significance of the electroencephalographic changes in hepatic coma. Trans Am Neurol Assoc, 1950. 51: p. 161-165. Cerca con Google

71. Frisancho, A.R., New norms of upper limb fat and muscle areas for assessment of nutritional status. Am J Clin Nutr, 1981. 34(11): p. 2540-5. Cerca con Google

72. Gebhardt, R., G. Beckers, F. Gaunitz, W. Haupt, et al., Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels. J Pharmacol Exp Ther, 1997. 283(1): p. 1-6. Cerca con Google

73. Georgiev, I., I. Lolova, T. Bojinova, On the correlation between the clinical and morphological findings in cases of benign pseudodystrophic forms of muscular atrophy. Neurol Psychiatr (Bucur), 1976. 14(1): p. 35-40. Cerca con Google

74. Gitlin, N., D.C. Lewis, L. Hinkley, The diagnosis and prevalence of subclinical hepatic encephalopathy in apparently healthy, ambulant, non-shunted patients with cirrhosis. J Hepatol, 1986. 3(1): p. 75-82. Cerca con Google

75. Gleckman, R.A., Urinary tract infection. Clin Geriatr Med, 1992. 8(4): p. 793-803. Cerca con Google

76. Groeneweg, M., J.C. Quero, B. De, I, I.J. Hartmann, et al., Subclinical hepatic encephalopathy impairs daily functioning. Hepatology, 1998. 28(1): p. 45-49. Cerca con Google

77. Guerit, J.M., A. Amantini, C. Fischer, P.W. Kaplan, et al., Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines. Liver Int, 2009. 29(6): p. 789-96. Cerca con Google

78. Guevara, M., M.E. Baccaro, A. Torre, B. Gomez-Anson, et al., Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis. Am J Gastroenterol, 2009. 104(6): p. 1382-9. Cerca con Google

79. Harper, A.E., Nutritional regulations and legislation--past developments, future implications. J Am Diet Assoc, 1977. 71(6): p. 601-609. Cerca con Google

80. Hass, H.G., T. Nagele, U. Seeger, F. Hosl, et al., [Detection of subclinical and overt hepatic encephalopathy and treatment control after L-ornithine-L-aspartate medication by magnetic resonance spectroscopy ((1)H-MRS)]. Z Gastroenterol, 2005. 43(4): p. 373-8. Cerca con Google

81. Hassanein, T.I., R.C. Hilsabeck, W. Perry, Introduction to the Hepatic Encephalopathy Scoring Algorithm (HESA). Dig Dis Sci, 2008. 53(2): p. 529-538. Cerca con Google

82. Haussinger, D., Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology, 2006. 43(6): p. 1187-1190. Cerca con Google

83. Hazell, A.S., R.F. Butterworth, Hepatic encephalopathy: An update of pathophysiologic mechanisms. Proc Soc Exp Biol Med, 1999. 222(2): p. 99-112. Cerca con Google

84. Heymsfield, S.B., C. McManus, J. Smith, V. Stevens, et al., Anthropometric measurement of muscle mass: revised equations for calculating bone-free arm muscle area. Am J Clin Nutr, 1982. 36(4): p. 680-90. Cerca con Google

85. Horne, J.A., O. Ostberg, A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol, 1976. 4(2): p. 97-110. Cerca con Google

86. Iguchi, H., K.I. Kato, H. Ibayashi, Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab, 1982. 54(5): p. 1025-7. Cerca con Google

87. Iles, J.F., J.J. Jack, Ammonia: assessment of its action on postsynaptic inhibition as a cause of convulsions. Brain, 1980. 103(3): p. 555-578. Cerca con Google

88. Iwasa, M., M. Kaito, Y. Adachi, Y. Watanabe, et al., Cerebral blood flow in basal ganglia is correlated with clinical signs of hepatic encephalopathy in patients with liver cirrhosis. Am J Gastroenterol, 2002. 97(3): p. 763-4. Cerca con Google

89. Jalan, R., J. Bernuau, Induction of cerebral hyperemia by ammonia plus endotoxin: does hyperammonemia unlock the blood-brain barrier? J Hepatol, 2007. 47(2): p. 168-171. Cerca con Google

90. Jasper, H.H., G. ARFEL-CAPDEVILLE, T. RASMUSSEN, Evaluation of EEG and cortical electrographic studies for prognosis of seizures following surgical excision of epileptogenic lesions. Epilepsia, 1961. 2: p. 130-137. Cerca con Google

91. Jepson, J.B., P. Zaltzman, S. Udenfriend, Microsomal hydroxylation of tryptamine, indoleacetic acid and related compounds, to 6-hydroxy derivatives. Biochim Biophys Acta, 1962. 62: p. 91-102. Cerca con Google

92. Jodynis-Liebert, J., J. Flieger, A. Matuszewska, J. Juszczyk, Serum metabolite/caffeine ratios as a test for liver function. J Clin Pharmacol, 2004. 44(4): p. 338-47. Cerca con Google

93. Johns, M.W., A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep, 1991. 14(6): p. 540-5. Cerca con Google

94. Johns, M.W., Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard. J Sleep Res, 2000. 9(1): p. 5-11. Cerca con Google

95. Johns, M.W., Sleep propensity varies with behaviour and the situation in which it is measured: the concept of somnificity. J Sleep Res, 2002. 11(1): p. 61-7. Cerca con Google

96. Kearns, P.J., H. Young, G. Garcia, T. Blaschke, et al., Accelerated improvement of alcoholic liver disease with enteral nutrition. Gastroenterology, 1992. 102(1): p. 200-205. Cerca con Google

97. Kircheis, G., R. Nilius, C. Held, H. Berndt, et al., Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology, 1997. 25(6): p. 1351-60. Cerca con Google

98. Kircheis, G., M. Wettstein, S. Dahl, D. Haussinger, Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Metab Brain Dis, 2002. 17(4): p. 453-62. Cerca con Google

99. Klein, D.C., J.L. Weller, Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science, 1970. 169(950): p. 1093-5. Cerca con Google

100. Knowles, J.B., A.W. MacLean, L. Salem, C. Vetere, et al., Slow-wave sleep in daytime and nocturnal sleep: an estimate of the time course of "Process S". J Biol Rhythms, 1986. 1(4): p. 303-8. Cerca con Google

101. Kreis, R., B.D. Ross, N.A. Farrow, Z. Ackerman, Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. Radiology, 1992. 182(1): p. 19-27. Cerca con Google

102. Kullmann, F., S. Hollerbach, G. Lock, A. Holstege, et al., Brain electrical activity mapping of EEG for the diagnosis of (sub)clinical hepatic encephalopathy in chronic liver disease. Eur J Gastroenterol Hepatol, 2001. 13(5): p. 513-522. Cerca con Google

103. Kunin, C.M., T.C. Chalmers, C.M. Leevy, S.C. Sebastyen, et al., Absorption of orally administered neomycin and kanamycin with special reference to patients with severe hepatic and renal disease. N Engl J Med, 1960. 262: p. 380-5. Cerca con Google

104. Kurtz, D., J.P. Zenglein, M. Imler, M. Girardel, et al., [Night sleep in porto-caval encephalopathy]. Electroencephalogr Clin Neurophysiol, 1972. 33(2): p. 167-78. Cerca con Google

105. Lai, J.C., A.J. Cooper, Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem, 1986. 47(5): p. 1376-1386. Cerca con Google

106. Landolt, H.P., Sleep homeostasis: a role for adenosine in humans? Biochem Pharmacol, 2008. 75(11): p. 2070-9. Cerca con Google

107. Landolt, H.P., J.V. Retey, K. Tonz, J.M. Gottselig, et al., Caffeine attenuates waking and sleep electroencephalographic markers of sleep homeostasis in humans. Neuropsychopharmacology, 2004. 29(10): p. 1933-9. Cerca con Google

108. Laubenberger, J., D. Haussinger, S. Bayer, H. Gufler, et al., Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology, 1997. 112(5): p. 1610-1616. Cerca con Google

109. Lavoie, J., J.F. Giguere, G.P. Layrargues, R.F. Butterworth, Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J Neurochem, 1987. 49(3): p. 692-697. Cerca con Google

110. Lerner, A.B., J.J. Nordlund, Melatonin: clinical pharmacology. J Neural Transm Suppl, 1978(13): p. 339-47. Cerca con Google

111. Lewy, A.J., T.A. Wehr, F.K. Goodwin, D.A. Newsome, et al., Light suppresses melatonin secretion in humans. Science, 1980. 210(4475): p. 1267-9. Cerca con Google

112. Lockley, S.W., D.J. Skene, J. Arendt, Comparison between subjective and actigraphic measurement of sleep and sleep rhythms. J Sleep Res, 1999. 8(3): p. 175-83. Cerca con Google

113. Lockwood, A.H., Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis, 2004. 19(3-4): p. 345-349. Cerca con Google

114. Lockwood, A.H., J.M. McDonald, R.E. Reiman, A.S. Gelbard, et al., The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest, 1979. 63(3): p. 449-460. Cerca con Google

115. Lockwood, A.H., E.W. Yap, W.H. Wong, Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J Cereb Blood Flow Metab, 1991. 11(2): p. 337-341. Cerca con Google

116. Loguercio, C., R. Abbiati, M. Rinaldi, A. Romano, et al., Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J Hepatol, 1995. 23(1): p. 39-46. Cerca con Google

117. Lozeva, V., L. Tuomisto, J. Tarhanen, R.F. Butterworth, Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. J Hepatol, 2003. 39(4): p. 522-7. Cerca con Google

118. Luo, B., L. Liu, L. Tang, J. Zhang, et al., ET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats. Am J Physiol Gastrointest Liver Physiol, 2004. 286(2): p. G294-303. Cerca con Google

119. Macbeth, W.A., E.H. Kass, W.V. McDermott, Jr., Treatment of Hepatic Encephalopathy by Alteration of Intestinal Flora with Lactobacillus Acidophilus. Lancet, 1965. 1(7382): p. 399-403. Cerca con Google

120. Maier, K.P., H. Talke, W. Gerok, Activities of urea-cycle enzymes in chronic liver disease. Klin Wochenschr, 1979. 57(13): p. 661-5. Cerca con Google

121. Marchesini, G., G. Bianchi, P. Amodio, F. Salerno, et al., Factors associated with poor health-related quality of life of patients with cirrhosis. Gastroenterology, 2001. 120(1): p. 170-8. Cerca con Google

122. Marchesini, G., G. Bianchi, M. Merli, P. Amodio, et al., Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology, 2003. 124(7): p. 1792-801. Cerca con Google

123. Marchesini, G., A. Fabbri, G. Bianchi, M. Brizi, et al., Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology, 1996. 23(5): p. 1084-92. Cerca con Google

124. Marchetti, P., C. D'Avanzo, R. Orsato, S. Montagnese, et al., Electroencephalography in patients with cirrhosis. Gastroenterology, 2011. 141(5): p. 1680-9 e1-2. Cerca con Google

125. McDermott, W.V., R.D. Adams, Episodic Stupor Associated with an Eck Fistula in the Human with Particular Reference to the Metabolism of Ammoniaxs. J Clin Invest, 1954. 33(1): p. 1-9. Cerca con Google

126. Montagnese, S., A. Biancardi, S. Schiff, P. Carraro, et al., Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepathology, 2010: p. In press. Cerca con Google

127. Montagnese, S., C. Jackson, M.Y. Morgan, Spatio-temporal decomposition of the electroencephalogram in patients with cirrhosis. J Hepatol, 2007. 46(3): p. 447-58. Cerca con Google

128. Montagnese, S., B. Middleton, A.R. Mani, D.J. Skene, et al., Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome? Metab Brain Dis, 2009. 24(3): p. 427-39. Cerca con Google

129. Montagnese, S., B. Middleton, A.R. Mani, D.J. Skene, et al., On the origin and the consequences of circadian abnormalities in patients with cirrhosis. Am J Gastroenterol, 2010. 105(8): p. 1773-81. Cerca con Google

130. Montagnese, S., B. Middleton, D.J. Skene, M.Y. Morgan, Night-time sleep disturbance does not correlate with neuropsychiatric impairment in patients with cirrhosis. Liver Int, 2009. 29(9): p. 1372-82. Cerca con Google

131. Moore, R.Y., Neural control of the pineal gland. Behav Brain Res, 1996. 73(1-2): p. 125-30. Cerca con Google

132. Morgan, M.Y., A.W. Jakobovits, I.M. James, S. Sherlock, Successful use of bromocriptine in the treatment of chronic hepatic encephalopathy. Gastroenterology, 1980. 78(4): p. 663-70. Cerca con Google

133. Morgan, T.R., T.E. Moritz, C.L. Mendenhall, R. Haas, Protein consumption and hepatic encephalopathy in alcoholic hepatitis. VA Cooperative Study Group #275. J Am Coll Nutr, 1995. 14(2): p. 152-158. Cerca con Google

134. Moroni, F., R. Carpenedo, G. Mannaioni, A. Galli, et al., Studies on the pharmacological properties of oxindole (2-hydroxyindole) and 5-hydroxyindole: are they involved in hepatic encephalopathy? Adv Exp Med Biol, 1997. 420: p. 57-73. Cerca con Google

135. Moroni, F., R. Carpenedo, I. Venturini, M. Baraldi, et al., Oxindole in pathogenesis of hepatic encephalopathy. Lancet, 1998. 351(9119): p. 1861-. Cerca con Google

136. Mostacci, B., M. Ferlisi, A. Baldi Antognini, C. Sama, et al., Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case control study. Neurol Sci, 2008. 29(4): p. 237-40. Cerca con Google

137. Nobili, L., M. Ferrara, F. Moroni, L. De Gennaro, et al., Dissociated wake-like and sleep-like electro-cortical activity during sleep. Neuroimage, 2011. 58(2): p. 612-9. Cerca con Google

138. Norenberg, M.D., Z. Huo, J.T. Neary, A. Roig-Cantesano, The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: relation to energy metabolism and glutamatergic neurotransmission. Glia, 1997. 21(1): p. 124-33. Cerca con Google

139. Norenberg, M.D., Y. Itzhak, A.S. Bender, The peripheral benzodiazepine receptor and neurosteroids in hepatic encephalopathy. Adv Exp Med Biol, 1997. 420: p. 95-111. Cerca con Google

140. Norenberg, M.D., A.R. Jayakumar, K.V. Rama Rao, K.S. Panickar, New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis, 2007. 22(3-4): p. 219-234. Cerca con Google

141. Olde Damink, S.W., R. Jalan, N.E. Deutz, D.N. Redhead, et al., The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology, 2003. 37(6): p. 1277-1285. Cerca con Google

142. Ong, J.P., A. Aggarwal, D. Krieger, K.A. Easley, et al., Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med, 2003. 114(3): p. 188-93. Cerca con Google

143. Oppong, K.N., H. Al-Mardini, M. Thick, C.O. Record, Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study. Hepatology, 1997. 26(4): p. 870-6. Cerca con Google

144. Ott, P., F.S. Larsen, Blood-brain barrier permeability to ammonia in liver failure: a critical reappraisal. Neurochem Int, 2004. 44(4): p. 185-198. Cerca con Google

145. Parsons-Smith, B.G., W.H.J. Summerskill, A.M. Dawson, S. SHERLOCK, The electroencephalograph in liver disease. The Lancet, 1957. 2: p. 867-871. Cerca con Google

146. Pedersen, H.R., H. Ring-Larsen, N.V. Olsen, F.S. Larsen, Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes in cerebral hemodynamics in rats anaesthetised with pentobarbital. J Hepatol, 2007. 47(2): p. 245-52. Cerca con Google

147. Phillips, G.B., R. Schwartz, G.J. Gabuzda, Jr., C.S. Davidson, The syndrome of impending hepatic coma in patients with cirrhosis of the liver given certain nitrogenous substances. N Engl J Med, 1952. 247(7): p. 239-46. Cerca con Google

148. Poo, J.L., J. Gongora, F. Sanchez-Avila, S. Aguilar-Castillo, et al., Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study. Ann Hepatol, 2006. 5(4): p. 281-8. Cerca con Google

149. Pugh, R.N., I.M. Murray-Lyon, J.L. Dawson, M.C. Pietroni, et al., Transection of the oesophagus for bleeding oesophageal varices. Br J Surg, 1973. 60(8): p. 646-649. Cerca con Google

150. Quay, W.B., Circadian and Estrous Rhythms in Pineal Melatonin and 5-Hydroxy Indole-3-Acetic Acid. Proc Soc Exp Biol Med, 1964. 115: p. 710-3. Cerca con Google

151. Quero, J.C., S.W. Schalm, Subclinical hepatic encephalopathy. Semin Liver Dis, 1996. 16(3): p. 321-328. Cerca con Google

152. Raabe, W., Ammonium decreases excitatory synaptic transmission in cat spinal cord in vivo. J Neurophysiol, 1989. 62(6): p. 1461-1473. Cerca con Google

153. Raabe, W., Ammonium ions abolish excitatory synaptic transmission between cerebellar neurons in primary dissociated tissue culture. J Neurophysiol, 1992. 68(1): p. 93-99. Cerca con Google

154. Rechtschaffen, A., A. Kales, A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Bethesda, MD: National Institutes of Health, 1968. Cerca con Google

155. Rees, C.J., K. Oppong, H. Al Mardini, M. Hudson, et al., Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut, 2000. 47(4): p. 571-4. Cerca con Google

156. Retey, J.V., M. Adam, J.M. Gottselig, R. Khatami, et al., Adenosinergic mechanisms contribute to individual differences in sleep deprivation-induced changes in neurobehavioral function and brain rhythmic activity. J Neurosci, 2006. 26(41): p. 10472-9. Cerca con Google

157. Retey, J.V., M. Adam, E. Honegger, R. Khatami, et al., A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A, 2005. 102(43): p. 15676-81. Cerca con Google

158. Reynolds, N., S. Downie, K. Smith, G. Kircheis, et al., Treatment with L-ornithine-L-aspartate (LOLA) infusion restores muscle protein synthesis responsiveness to feeding in patients with cirrhosis. J Hepatol, 1999. 30((Suppl)): p. 65. Cerca con Google

159. Riggio, O., F. Ariosto, M. Merli, M. Caschera, et al., Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. Dig Dis Sci, 1991. 36(9): p. 1204-8. Cerca con Google

160. Riggio, O., C. Efrati, C. Catalano, F. Pediconi, et al., High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study. Hepatology, 2005. 42(5): p. 1158-65. Cerca con Google

161. Riggio, O., A. Masini, C. Efrati, F. Nicolao, et al., Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol, 2005. 42(5): p. 674-9. Cerca con Google

162. Riggio, O., L. Ridola, C. Pasquale, S. Nardelli, et al., Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol, 2011. 9(2): p. 181-3. Cerca con Google

163. Rikkers, L., P. Jenko, D. Rudman, D. Freides, Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology, 1978. 75(3): p. 462-469. Cerca con Google

164. Rolando, N., J. Wade, M. Davalos, J. Wendon, et al., The systemic inflammatory response syndrome in acute liver failure. Hepatology, 2000. 32(4 Pt 1): p. 734-739. Cerca con Google

165. Romero-Gomez, M., L. Grande, I. Camacho, Prognostic value of altered oral glutamine challenge in patients with minimal hepatic encephalopathy. Hepatology, 2004. 39(4): p. 939-43. Cerca con Google

166. Romero-Gomez, M., L. Grande, I. Camacho, S. Benitez, et al., Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. J Hepatol, 2002. 37(6): p. 781-7. Cerca con Google

167. Rose, C., A. Michalak, P. Pannunzio, G. Therrien, et al., L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis, 1998. 13(2): p. 147-57. Cerca con Google

168. Ross, B.D., S. Jacobson, F. Villamil, J. Korula, et al., Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities. Radiology, 1994. 193(2): p. 457-63. Cerca con Google

169. Rucci, P., G. Taliani, L. Cirrincione, A. Alberti, et al., Validity and reliability of the Italian version of the Chronic Liver Disease Questionnaire (CLDQ-I) for the assessment of health-related quality of life. Dig Liver Dis, 2005. 37(11): p. 850-60. Cerca con Google

170. Sagales, T., V. Gimeno, M.D. de la Calzada, F. Casellas, et al., Brain mapping analysis in patients with hepatic encephalopathy. Brain Topogr, 1990. 2(3): p. 221-8. Cerca con Google

171. Sakurabayashi, S., S. Sezai, Y. Yamamoto, M. Hirano, et al., Embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy. Cardiovasc Intervent Radiol, 1997. 20(2): p. 120-4. Cerca con Google

172. Saper, C.B., T.E. Scammell, J. Lu, Hypothalamic regulation of sleep and circadian rhythms. Nature, 2005. 437(7063): p. 1257-63. Cerca con Google

173. Scott, N.R., D. Stambuk, J. Chakraborty, V. Marks, et al., The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease. Br J Clin Pharmacol, 1989. 27(2): p. 205-13. Cerca con Google

174. Sharma, P., B.C. Sharma, S.K. Sarin, Predictors of nonresponse to lactulose for minimal hepatic encephalopathy in patients with cirrhosis. Liver Int, 2009. 29(9): p. 1365-71. Cerca con Google

175. Shawcross, D., R. Jalan, The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci, 2005. 62(19-20): p. 2295-304. Cerca con Google

176. Sherlock, S., W.H. Summerskill, L.P. White, E.A. Phear, Portal-systemic encephalopathy; neurological complications of liver disease. Lancet, 1954. 267(6836): p. 454-457. Cerca con Google

177. Staedt, U., H. Leweling, R. Gladisch, C. Kortsik, et al., Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol, 1993. 19(3): p. 424-30. Cerca con Google

178. Stauch, S., G. Kircheis, G. Adler, K. Beckh, et al., Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol, 1998. 28(5): p. 856-64. Cerca con Google

179. Steindl, P.E., P. Ferenci, W. Marktl, Impaired hepatic catabolism of melatonin in cirrhosis. Ann Intern Med, 1997. 127(6): p. 494. Cerca con Google

180. Steindl, P.E., B. Finn, B. Bendok, S. Rothke, et al., Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann Intern Med, 1995. 123(4): p. 274-7. Cerca con Google

181. Strauss, E., R. Tramote, E.P. Silva, W.R. Caly, et al., Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology, 1992. 39(6): p. 542-5. Cerca con Google

182. Such, J., R. Frances, C. Munoz, P. Zapater, et al., Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology, 2002. 36(1): p. 135-41. Cerca con Google

183. Sushma, S., S. Dasarathy, R.K. Tandon, S. Jain, et al., Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology, 1992. 16(1): p. 138-44. Cerca con Google

184. Szerb, J.C., R.F. Butterworth, Effect of ammonium ions on synaptic transmission in the mammalian central nervous system. Prog Neurobiol, 1992. 39(2): p. 135-153. Cerca con Google

185. Takashi, M., M. Igarashi, S. Hino, K. Takayasu, et al., Portal hemodynamics in chronic portal-systemic encephalopathy. Angiographic study in seven cases. J Hepatol, 1985. 1(5): p. 467-76. Cerca con Google

186. Tarter, R.E., A.M. Hegedus, D.H. Van Thiel, Neuropsychiatric sequelae of portal-systemic encephalopathy: a review. Int J Neurosci, 1984. 24(3-4): p. 203-216. Cerca con Google

187. Taylor-Robinson, S.D., J. Sargentoni, C.D. Marcus, M.Y. Morgan, et al., Regional variations in cerebral proton spectroscopy in patients with chronic hepatic encephalopathy. Metab Brain Dis, 1994. 9(4): p. 347-59. Cerca con Google

188. Teasdale, G., B. Jennett, Assessment of coma and impaired consciousness. A practical scale. Lancet, 1974. 2(7872): p. 81-84. Cerca con Google

189. Trzepacz, P.T., R.E. Tarter, A. Shah, R. Tringali, et al., SPECT scan and cognitive findings in subclinical hepatic encephalopathy. J Neuropsychiatry Clin Neurosci, 1994. 6(2): p. 170-5. Cerca con Google

190. Van Caulaert, C., C. Deviller, Ammoniémie expérimentale aprés ingestion de chlorure d'ammonium chez l'homme à l'état normal et pathologique. C R Soc Biol (Paris), 1932. 111: p. 50. Cerca con Google

191. Van der Rijt, C.C., S.W. Schalm, G.H. De Groot, M. De Vlieger, Objective measurement of hepatic encephalopathy by means of automated EEG analysis. Electroencephalogr Clin Neurophysiol, 1984. 57(5): p. 423-426. Cerca con Google

192. van Leeuwen, P.A., C.L. van Berlo, P.B. Soeters, New mode of action for lactulose. Lancet, 1988. 1(8575-6): p. 55-6. Cerca con Google

193. Venturini, I., L. Corsi, R. Avallone, F. Farina, et al., Ammonia and endogenous benzodiazepine-like compounds in the pathogenesis of hepatic encephalopathy. Scand J Gastroenterol, 2001. 36(4): p. 423-5. Cerca con Google

194. Victor, M., R.D. Adams, M. Cole, The acquired (non-Wilsonian) type of chronic hepatocerebral degeneration. Medicine (Baltimore), 1965. 44(5): p. 345-396. Cerca con Google

195. Vogels, B.A., B. van Steynen, M.A. Maas, G.G. Jorning, et al., The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy. J Hepatol, 1997. 26(2): p. 387-95. Cerca con Google

196. Ware, J.E., Jr., C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83. Cerca con Google

197. Watanabe, A., Cerebral changes in hepatic encephalopathy. J Gastroenterol Hepatol, 1998. 13(7): p. 752-60. Cerca con Google

198. Webb, W.B., H.W. Agnew, Jr., Stage 4 sleep: influence of time course variables. Science, 1971. 174(16): p. 1354-6. Cerca con Google

199. Weissenborn, K., J.C. Ennen, H. Schomerus, N. Ruckert, et al., Neuropsychological characterization of hepatic encephalopathy. J Hepatol, 2001. 34(5): p. 768-773. Cerca con Google

200. Werth, E., D.J. Dijk, P. Achermann, A.A. Borbely, Dynamics of the sleep EEG after an early evening nap: experimental data and simulations. Am J Physiol, 1996. 271(3 Pt 2): p. R501-10. Cerca con Google

201. Weyerbrock, A., J. Timmer, F. Hohagen, M. Berger, et al., Effects of light and chronotherapy on human circadian rhythms in delayed sleep phase syndrome: cytokines, cortisol, growth hormone, and the sleep-wake cycle. Biol Psychiatry, 1996. 40(8): p. 794-7. Cerca con Google

202. Wilkinson, D.J., N.J. Smeeton, P.W. Watt, Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol, 2010. 91(3): p. 200-19. Cerca con Google

203. Wiltfang, J., W. Nolte, J. von Heppe, E. Bahn, et al., Sleep disorders and portal-systemic encephalopathy following transjugular intrahepatic portosystemic stent shunt in patients with liver cirrhosis. Relation to plasma tryptophan. Adv Exp Med Biol, 1999. 467: p. 169-76. Cerca con Google

204. Wirtz-Justice, A., F. Benedetti, M. Terman, Chronotherapeutics for Affective Disorders. Ed. Karger, Milano, 2009. Cerca con Google

205. Yamamoto, M., M. Iwasa, K. Matsumura, Y. Nakagawa, et al., Improvement of regional cerebral blood flow after oral intake of branched-chain amino acids in patients with cirrhosis. World J Gastroenterol, 2005. 11(43): p. 6792-9. Cerca con Google

206. Yao, K.Q., Q.M. Qu, H.P. Lei, Effect of (+/-)-, (+)- and (-)-gossypol on the lactate dehydrogenase-X activity of rat testis. J Ethnopharmacol, 1987. 20(1): p. 25-29. Cerca con Google

207. Younossi, Z.M., G. Guyatt, M. Kiwi, N. Boparai, et al., Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut, 1999. 45(2): p. 295-300. Cerca con Google

208. Zieve, L., The mechanism of hepatic coma. Hepatology, 1981. 1(4): p. 360-365. Cerca con Google

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