Markers of reversible hepatic encephalopathy.
Explore the source record for details and available documents.
Hepatic Encephalopathy↗
Biomedical subjects
S Krieger
Publications and source records attributed to S Krieger.
Effect of tetrahydroaminoacridine on sleep in healthy subjects.
The present study investigated the impact of the cholinesterase inhibitor tetrahydroaminoacridine (THA; tacrine) on sleep in healthy subjects. According to the reciprocal interaction model of non-rapid eye movement (NREM) and REM sleep regulation, which postulates a primary role in cholinergic neurotransmission for the initiation and maintenance of REM sleep, it was expected that THA would lead to an earlier onset of REM sleep. In 12 healthy subjects aged from 21 to 50 years two different doses (20 mg, 40 mg) were administered 1 hour prior to bed time and compared to placebo. Only the higher dose of THA significantly shortened REM latency. No other significant effects on sleep architecture were observed, although administration of 40 mg tacrine was associated with a decrease in sleep efficiency and a prolongation of sleep latency. Blood plasma levels of tacrine and its metabolite 1-hydroxytacrine measured prior to sleep and during the first 90 min of sleep were significantly correlated with the onset of REM sleep in relation to the timing of drug administration (only for the 20 mg dose). The reversible cholinesterase inhibitor THA exerts effects on REM latency comparable to those observed with other cholinomimetic agents.
Adult↗
Attenuated familial adenomatous polyposis due to a mutation in the 3' part of the APC gene. A clue for understanding the function of the APC protein.
The identification of germline mutations in a large number of clinically well-characterised patients with familial adenomatous polyposis (FAP) has allowed the unravelling of several genotype-phenotype relationships that can now be interpreted in the light of the structure and functional domains of the adenomatous polyposis coli (APC) protein. An attenuated phenotype has been found to be associated with mutations at the 5' end of the gene, while a severe clinical expression was found in patients with the most common mutation at codon 1309. So far, only few mutations in the 3' half of the gene have been published. We report on two families with a rather mild phenotype due to a frameshift mutation at codon 1597. These families may represent a clue for defining a 5' border for the occurrence of a second region of attenuated FAP that is localised in the 3' part of the APC gene. We propose a model to explain the relationship between the severity of the disease and the size of the mutant APC protein.
Adenomatous Polyposis Coli↗
Cognitive dysfunction in schizophrenia: comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs.
Impaired cognitive function is both a feature of schizophrenia and a side effect of conventional neuroleptics. Maze tests were used to determine the effects on cognition of conventional dopamine antagonist neuroleptics (haloperidol and fluphenazine) and the newer serotonin-dopamine antagonist antipsychotics (risperidone and clozapine). Patients on clozapine or risperidone showed better performance on the maze tasks than untreated patients or patients taking conventional neuroleptics. In particular, patients treated with risperidone or clozapine were better able to maintain motor coordination while they focused on the more complex "frontal" maze tasks which required sequencing and planning. In view of the restrictions on the use of clozapine, it is suggested that risperidone should be more widely used in schizophrenia because it preserves cognitive function better than conventional neuroleptics and is therefore likely to allow patients to have better insight into their illness and to have better long-term quality of life expectations.
Clozapine↗
Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis.
BACKGROUND & AIMS: Hyperintense globus pallidus on T1-weighted magnetic resonance images (MRIs) in cirrhotic patients are reported to reflect severity of liver disease; however, their consequence for hepatic encephalopathy is unknown. The aim of this study was to outline a pattern of neuropsychiatric abnormalities in chronic liver failure and its correlation with MRI findings. METHODS: Fifty-one consecutive patients were enrolled in the study. Neuropsychiatric assessment used a standardized protocol, including dichotomized neurological parameters, brief psychiatric rating and psychometric tests, as well as electroencephalography. The severity of liver failure was graded using standard laboratory parameters and the Child-Pugh's classification. Signal intensity of the globus pallidus was determined on sagittal T1-weighted MRIs. RESULTS: Two aspects of neurological dysfunction could be distinguished by principal components analysis: impairment of complex cerebral function and subcortical motor performance. Both neurological categories correlated with severity of liver failure, grade of electroencephalographic abnormalities, and psychometric test results. Additionally, prior bouts of overt encephalopathy indicate progressive dementia. T1-weighted globus pallidus signal intensity did not correlate with any clinical or laboratory test result. CONCLUSIONS: This study shows a characteristic pattern of neurological findings in patients with liver failure and hyperintense globus pallidus on T1-weighted MRIs. Although neurological dysfunction parallels hepatic failure, MRI abnormalities of basal ganglia do not indicate severity of actual hepatic encephalopathy.
Adolescent↗
Cortical hyperintensity on proton density-weighted images: An MR sign of cyclosporine-related encephalopathy.
PURPOSE: To describe cortical hyperintensities in proton density-weighted images in six patients with presumed cyclosporine-induced neurotoxicity. METHODS: In six patients with clinical evidence of cyclosporine-related encephalopathy, MR imaging was performed after the onset of symptoms and signs (mean, 24 days after liver transplantation). Five of these patients had serial MR imaging for a period that varied from 2 to 20 months. Along with the imaging studies, the patients' clinical status was evaluated and various laboratory parameters, including blood pressure and levels of cyclosporine, cholesterol, and magnesium, were monitored. RESULTS: In all six patients, initial MR studies showed hyperintensity of several cerebral gyri that was unequivocal only on proton density-weighted images. Although in five patients these signal abnormalities were limited to the cortex, one patient had increased signal in the subjacent white matter as well. In one patient, the images were also remarkable for areas of cortical hyperintensities on T1-weighted images. In another patient, cortical enhancement occurred after administration of gadopentetate dimeglumine, with a normal cortical signal on the precontrast images. The abnormal cortical signal began to fade after cyclosporine reduction, but in two patients it remained visible for at least 20 months. The neurologic symptomatology associated with cyclosporine-induced neurotoxicity included seizures (three patients), speech disorder (three patients), and disturbance of consciousness (three patients). CONCLUSION: Cyclosporine-induced neurotoxicity occurring in patients after liver transplantation appears to affect the cerebral cortex preferentially. Because its MR equivalent resembles changes resulting from hypoxic injury or cortically centered vasculitis, we suspect the underlying mechanism may be a vascular injury that results in cortical hypoperfusion.
Adolescent↗
Induction of cytokine synthesis and fever suppresses REM sleep and improves mood in patients with major depression.
Beneficial effects of inflammatory events on certain psychiatric disorders, including depression, were reported sporadically by ancient Greek physicians, but have been described also in our times by a few psychiatrists during the past decades. During febrile inflammatory events, mediators of the immune system such as interleukin-1 can be detected in the brain and may act on their respective receptors which have also been demonstrated in the brain. Since cytokines such as interleukin-1 have been shown in animal studies to exert sedative behavioral effects, to be somnogenic, and to induce slow-wave sleep (SWS), we performed a pilot study to evaluate scientifically the anecdotically reported beneficial effects of inflammatory states on depressive disorders. Mood and sleep parameters were monitored in seven drug-free, severely depressed patients before, during, and after the administration of a single dose of endotoxin. All patients responded with a short pulse of increased synthesis of the cytokines tumor necrosis factor, interleukin-1, and interleukin-6 and elevated body temperature for several hours. During the night following endotoxin administration, rapid eye movement (REM) sleep was significantly suppressed, while changes in slow wave sleep were not significant. During the next day, all patients were in a significantly improved mood; however a rebound of REM sleep was observed in the second night after endotoxin administration and mood worsened again during the next days, indicating an only transient beneficial effect of the treatment.
Adult↗
Manganese and chronic hepatic encephalopathy.
Clinical observations and animal studies have raised the hypothesis that increased concentrations of manganese (Mn) in whole blood might lead to accumulation of this metal within the basal ganglia in patients with end-stage liver disease. We studied ten patients with liver failure (and ten controls) by magnetic resonance imaging (MRI) and measurement of Mn in brain tissue of three patients who died of progressive liver failure (and three controls) was also done. Whole blood Mn concentrations in patients with liver cirrhosis were significantly increased (median 34.4 micrograms/L vs 10.3 micrograms/L in controls; p = 0.0004) and pallidal signal intensity indices correlated with blood Mn (Rs = 0.8, p = 0.0058). Brain tissue samples reveal highest Mn concentrations in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus. Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between Mn neurotoxicity and chronic hepatic encephalopathy suggest that this metal may have a role in the pathogenesis of chronic hepatic encephalopathy. Further studies are warranted because the use of chelating agents could prove to be a new therapeutic option to prevent or reverse this neuropsychiatric syndrome.
Adult↗
[Age dependence of interleukin 6 and acute phase proteins].
In 59 healthy subjects of different age groups with no signs of inflammatory processes, the basal II-6 levels were measured. The II-6 concentrations were significantly higher in the oldest group (66-90 years) than in the two other age groups (24-40, 41-65 years). A positive correlation was found between age and II-6 concentration (r = 0.470). Otherwise, a statistically detectable relationship was found merely with alpha-2-macroglobulin and with total and LDL cholesterol.
Acute-Phase Proteins↗
Some considerations on estimating event-related brain signals.
Understanding the timing of mental acts is one of the prominent questions in information processing research. The analysis of event related potentials (ERP) with their high temporal resolution might make access to cognition related brain activity possible. We consider three major problems which make the application of ERPs questionable and then propose some solutions to these problems. The primary problem concerns the separation of the ERPs from the background EEG which is not related to the stimulus. The most common method used is averaging. We argue that this is not the most appropriate method and suggest an alternative for estimating the signal in single-trial recordings. Artifacts present a second problem. We will first review established methods of dealing with eye-movement artifacts and then propose an alternative. We will also report on current work on the parametrisation of single-trial signal estimates, which constitute the third problem considered.
Algorithms↗
Role of 3'-untranslated regions in the regulation of hexose transporter mRNAs in Trypanosoma brucei.
Trypanosoma brucei is a unicellular parasite that is transmitted from one mammalian host to the next by tsetse flies. The expression of many trypanosome genes is regulated during the life cycle but there is no evidence for developmental control of transcription by RNA polymerase II. T. brucei expresses at least two hexose transporter mRNAs that are developmentally regulated; we show here that specific portions of the 3'-untranslated regions are responsible for the differential expression. Different trypanosome 3'-untranslated regions, from surface protein, phosphoglycerate kinase and aldolase genes as well as the hexose transporter genes, conferred a spectrum of levels of reporter gene expression, and these activities differed between bloodstream forms and the procyclic forms that replicate in the tsetse vector. Experiments with permanently transformed cell lines showed that regulation occurs at the mRNA level. The results suggest that post-transcriptional control of mRNAs in trypanosomatids operates at several levels, and that it will not always be possible to attribute all the regulation to short RNA motifs.
Animals↗
Interleukin-6 serum levels in healthy persons correspond to the sleep-wake cycle.
Explore the source record for details and available documents.
Activity Cycles↗
Sleep EEG of patients with obsessive-compulsive disorder.
Twenty-two patients suffering from an obsessive and compulsive disorder (OCD) according to DSM-III-R were investigated by polysomnographic sleep EEG recordings under drug-free conditions and compared to age- and sex-matched healthy controls. Sleep efficiency was significantly lower and wake % SPT was significantly increased in the patient group compared to healthy subjects. Sleep architecture did not differ among the two samples. Especially REM sleep measures, in particular, REM latency did not differ among the groups. No positive correlation was found between sleep variables and rating inventories for obsession and compulsions (Y-BOCS), depression (Hamilton) and anxiety (CAS). A secondary depression did not influence sleep EEG variables. The results of this study contradict the assumption that OCD patients show REM sleep and slow wave sleep abnormalities similar to those shown by patients with primary depression.
Adult↗
Influence of biperiden and bornaprine on sleep in healthy subjects.
Biperiden, 4 mg, an anticholinergic drug that is relatively selective for the M1 receptor subtype, and bornaprine, 4 mg, a nonselective M1 and M2 antagonist, were administered orally in a randomized, double-blind design to twelve healthy volunteers to investigate the effect on polysomnographically recorded sleep. Both drugs suppressed rapid eye movement (REM) sleep as reflected by an increase of REM latency and a decrease in the percentage of REM sleep period time with the effects of biperiden being more pronounced. No significant effect on slow wave sleep was observed. The results of this study support the hypothesis that both the M1 and the M2 receptor subtype are involved in the regulation of REM sleep in humans.
Adult↗
Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans.
A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.
Adult↗
Frequency of ventricular ectopic activity in isolated systolic systemic hypertension.
Explore the source record for details and available documents.
Aged↗
Subjective and clinical results after transurethral resection and suprapubic prostatectomy in benign prostatic hypertrophy.
This study was performed after a mean postoperative period of approximately 2 years. Results after transurethral resection (TUR) appeared to be inferior to results after suprapubic prostatectomy in patients' subjective symptomatology concerning frequency, nocturia, urinary stream complaints and incontinence. Late postoperative complications were found in a greater extent after TUR. TUR showed more often pathologic uroflow and pathologic residual urine data. Generally speaking, the results after suprapubic prostatectomy were substantially more satisfactory than the results after TUR.
Aged↗
Recording automatic and controlled information processing by means of bioelectrical brain signals in normals and paranoid schizophrenics with and without neuroleptic medication.
Explore the source record for details and available documents.
Adult↗