RESUMEN
Visual working memory (VWM) is an active representation enabling the manipulation of item information even in the absence of visual input. A common way to investigate VWM is to analyze the performance at later recall. This approach, however, leaves uncertainties about whether the variation of recall performance is attributable to item encoding and maintenance or to the testing of memorized information. Here, we record the contralateral delay activity (CDA), an established electrophysiological measure of item storage and maintenance, in human subjects performing a delayed orientation precision estimation task. This allows us to link the fluctuation of recall precision directly to the process of item encoding and maintenance. We show that for two sequentially encoded orientation items, the CDA amplitude reflects the precision of orientation recall of both items, with higher precision being associated with a larger amplitude. Furthermore, we show that the CDA amplitudes for the items vary independently from each other, suggesting that the precision of memory representations fluctuates independently.NEW & NOTEWORTHY The present work demonstrates for the first time that the contralateral delay activity (CDA), an online electrophysiological measure of the number of representations maintained in memory, is also a reliable measure of the precision of memory representations. Furthermore, we show that the CDA fluctuates independently for individual items held in memory, thereby providing unambiguous direct neurophysiological support for independently fluctuating memory representations.
Asunto(s)
Corteza Cerebral/fisiología , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Reconocimiento Visual de Modelos/fisiología , Memoria Espacial/fisiología , Adulto , Electroencefalografía , Humanos , Adulto JovenRESUMEN
BACKGROUND: Teledermoscopy is a promising modern technique to complement or to substitute dermatologic examination. OBJECTIVE: In this pilot study, we compared the outcomes of teledermoscopic consultations with clinical examinations and histologic results. METHODS: Conventional and dermatoscopic photos of single lesions were taken in 26 patients using a mobile phone and an attached handyscope optical system. Five resident physicians performed a clinical examination including dermoscopy while the teledermatologic and teledermoscopic photos were assessed by an experienced dermatologist. Examination results were compared regarding diagnosis, differential diagnoses, recommended further management, as well as subjective and objective accuracy of diagnosis. In addition, 23% of the lesions were excised and histologically examined. RESULTS: The most frequent diagnosis was "nevus cell nevus", followed by "subungual hematoma" and "basal cell carcinoma". The concordance of diagnoses was 92.3%; the concordance of recommended further management was 76.9%. Of the 6 histologically proven diagnoses, 66.7% were given the same diagnosis by teledermatoscopy and conventional clinical assessment. Concerning accuracy of diagnosis, teledermoscopy showed no disadvantage. CONCLUSIONS: Teledermatologic photos of single lesions combined with teledermatoscopic photos can be reliably and safely assessed. Especially when access to dermatologic examination is difficult, mobile teledermoscopy is a good and reliable alternative.
Asunto(s)
Dermoscopía/instrumentación , Hematoma/diagnóstico , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutáneas/diagnóstico , Teléfono Inteligente , Telemedicina/instrumentación , Diseño de Equipo , Alemania , Humanos , Melanoma/patología , Nevo Pigmentado/patología , Proyectos Piloto , Garantía de la Calidad de Atención de Salud , Reproducibilidad de los Resultados , Piel/patología , Neoplasias Cutáneas/patologíaRESUMEN
The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne-Östberg (HÖ). The aim of the present study was to assess the reliability of a subject's self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HÖ (Self-ME). A convenience sample of 461 subjects [23.8 ± 4.7 years; 322 females] completed a full sleep-wake assessment, including diurnal preference (HÖ), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep-wake timing (12 d sleep diaries; n = 296). Significant differences in HÖ total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p < 0.0001). Significant differences in sleep-wake timing (bed time, try to sleep and sleep onset, wake up, and get up time) were observed between Self-ME classes. Such differences were maintained when sleep-wake habits were analysed separately on work and free days, and also in a smaller group of 67 subjects who completed the Self-ME as a stand-alone rather than as part of the original questionnaire. Significant differences were observed in the time-course of subjective sleepiness by Self-ME class in both the large and the small group, with Self-MM and Self-M subjects being significantly more alert in the morning and sleepier in the evening hours compared with their Self-E and Self-EE counterparts. Finally, significant differences were observed in night sleep quality between Self-ME classes, with Self-EE/Self-E subjects sleeping worse than their Self-MM/Self-M counterparts, and averaging just over the abnormality PSQI threshold of 5. In conclusion, young, healthy adults can define their diurnal preference based on a single question (Self-ME) in a way that reflects their sleep-wake timing, their sleepiness levels over the daytime hours, and their night sleep quality. Validation of the Self-ME across the decades and in diseased populations seems worthy.
Asunto(s)
Ciclos de Actividad , Relojes Circadianos/fisiología , Autoevaluación (Psicología) , Sueño , Encuestas y Cuestionarios , Vigilia , Adolescente , Adulto , Anciano , Niño , Femenino , Hábitos , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de Tiempo , Adulto JovenRESUMEN
Amazingly, human observers can track four independently moving targets. The present study investigated the neural correlates of multiple-object tracking (MOT). Based on previous work we used a modified MOT-task to which subjects exhibited different behaviors. One half of the subjects showed slower RTs and higher error rates with increasing correspondence between tracked items and a probe consisting of 4 highlighted items presented after the tracking. The other half of the subjects had better performance when the probe fully matched the tracked items. Here we sought to investigate the neural representation of the two divergent behavior types. Using multivariate pattern analysis we observed two partly overlapping functional networks associated with the different behaviors. Subjects that responded fast and accurate to full-congruity trials predominantly showed a functional pattern for the full-congruity condition that was very different from patterns associated with any of the partly congruent conditions. This "deviant" pattern was observed in frontal, parietal and extrastriate visual brain areas. In the group of subjects with decreasing performance for increasing target-probe congruity these same regions exhibited a very different functional relationship, in which increasing congruities were associated with linearly changing neural activity patterns. Early low-tier visual areas exclusively exhibited the linear classification pattern while area LO and the primary motor cortex exclusively showed the deviant pattern across all subjects. The coexistence of both networks in groups with different behaviors provides the neural basis for a flexible behavior that can be flexibly adjusted as a function of the strategy employed in the task.
Asunto(s)
Encéfalo/fisiología , Percepción de Movimiento/fisiología , Reconocimiento Visual de Modelos/fisiología , Adulto , Mapeo Encefálico , Humanos , Individualidad , Imagen por Resonancia Magnética , Corteza Motora/fisiología , Análisis Multivariante , Lóbulo Occipital/fisiología , Desempeño Psicomotor , Tiempo de Reacción , Adulto JovenRESUMEN
Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH.
Asunto(s)
Anticuerpos Antineoplásicos/sangre , Antígenos de Neoplasias/inmunología , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/complicaciones , Inmunoglobulina M/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Serpinas/inmunología , Adolescente , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/patología , Adulto JovenRESUMEN
UNLABELLED: Hyperammonaemia is observed after prolonged, intense exercise, or in patients with hepatic failure. In the latter, it is associated with a set of neurological and psychiatric abnormalities termed hepatic encephalopathy. THE AIMS OF OUR STUDY WERE: 1. to measure vigilance in a condition of induced hyperammonaemia; 2. to assess whether caffeine modulates the effects of hyperammonaemia on vigilance, if any. Ten healthy volunteers (28.5 ± 5 years; 5 males) underwent three experimental sessions consisting of two-hourly measurements of capillary ammonia, subjective sleepiness (Karolinska Sleepiness Scale) and vigilance (Psychomotor Vigilance Task, PVT), in relation to the intake of breakfast (+/-coffee), an amino acid mixture which induces hyperammonaemia (amino acid challenge; AAC), and AAC+coffee (only for participants who had coffee with their standard breakfast). The AAC resulted in: 1. the expected increase in capillary ammonia levels, with highest values at approximately 4 h after the administration; 2. a significant increase in subjective sleepiness ratings; 3. a sustained increase in PVT-based reaction times. When caffeine was administered after the AAC, both subjective sleepiness and the slowing in RTs were significantly milder than in the AAC-only condition. In conclusion, acute hyperammonaemia induces an increase in subjective sleepiness and a sustained decrease in vigilance, which are attenuated by the administration of a single espresso coffee.
Asunto(s)
Nivel de Alerta/efectos de los fármacos , Cafeína/uso terapéutico , Hiperamonemia/psicología , Desempeño Psicomotor/efectos de los fármacos , Enfermedad Aguda , Adulto , Aminoácidos/toxicidad , Desayuno , Capilares , Café , Humanos , Hiperamonemia/sangre , Hiperamonemia/inducido químicamente , Hiperamonemia/tratamiento farmacológico , Masculino , Registros Médicos , Adulto JovenRESUMEN
Approximately 90% of melanomas retain wild-type p53, a characteristic that may help shape the development of novel treatment strategies. Here, we employed an adenoviral vector where transgene expression is controlled by p53 to deliver the p19 alternate reading frame (Arf) and interferon-ß (IFNß) complementary DNAs in the B16 mouse model of melanoma. In vitro, cell death was enhanced by combined gene transfer (63.82±15.30% sub-G0 cells); yet introduction of a single gene resulted in significantly fewer hypoploid cells (37.73±7.3% or 36.96±11.58%, p19Arf or IFNß, respectively, P<0.05). Annexin V staining and caspase-3 cleavage indicate a cell death mechanism consistent with apoptosis. Using reverse transcriptase quantitative PCR, we show that key transcriptional targets of p53 were upregulated in the presence of p19Arf, although treatment with IFNß did not alter expression of the genes studied. In situ gene therapy revealed significant inhibition of subcutaneous tumors by IFNß (571±25 mm3) or the combination of p19Arf and IFNß (489±124 mm3) as compared with the LacZ control (1875±33 mm3, P<0.001), whereas p19Arf yielded an intermediate result (1053±169 mm3, P<0.01 vs control). However, only the combination was associated with increased cell death and prolonged survival (P<0.01). As shown here, the combined transfer of p19Arf and IFNß using p53-responsive vectors enhanced cell death both in vitro and in vivo.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Interferón beta/genética , Melanoma Experimental/genética , Melanoma Experimental/terapia , Animales , Apoptosis/genética , Muerte Celular/genética , Línea Celular Tumoral , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Modelos Animales de Enfermedad , Femenino , Interferón beta/biosíntesis , Interferón beta/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Transducción GenéticaRESUMEN
OBJECTIVE: To study the effect of hyperammonaemia on the wake electroencephalogram (EEG) of patients with cirrhosis and healthy volunteers. METHODS: Wake EEGs were recorded prior to and after the induction of controlled hyperammonaemia in 10 patients with cirrhosis and 10 matched healthy volunteers. RESULTS: At baseline, patients had higher ammonaemia than healthy volunteers and their dominant EEG rhythm was slower and of higher amplitude. Induced hyperammonaemia resulted in increased spectral power over most of the scalp in healthy volunteers and decreased frequency along the anterior-posterior midline in patients. CONCLUSIONS: These findings suggest different effects of hyperammonaemia on the wake EEG in relation to baseline/peak ammonia levels. SIGNIFICANCE: The wake EEG is sensitive to hyperammonaemia and power-based EEG parameters may help in its neurophysiological definition, which, to date, has generally been based on EEG frequency indices.
Asunto(s)
Corteza Cerebral/fisiopatología , Encefalopatía Hepática/fisiopatología , Hiperamonemia/fisiopatología , Cirrosis Hepática/fisiopatología , Adulto , Anciano , Mapeo Encefálico , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Attention to specific features of moving visual stimuli modulates the activity in human cortical motion sensitive areas. In this study we employed combined event-related electrophysiological, magnetencephalographic (EEG, MEG) and hemodynamic functional magnetic resonance imaging (fMRI) measures of brain activity to investigate the precise time course and the neural correlates of feature-based attention to speed and coherence. Subjects were presented with an aperture of dots randomly moving either slow or fast, at the same time displaying a high or low level of coherence. The task was to attend either the speed or the coherence and press a button upon the high speed or high coherence stimulus respectively. When attention was directed to the speed of motion enhanced neural activity was found in the dorsal visual area V3a and in the IPL, areas previously shown to be specialized for motion processing. In contrast, when attention was directed to the coherence of motion significant hemodynamic activity was observed in the parietal areas fIPS and SPL that are specialized for the processing of complex motion patterns. Concurrent recordings of the event-related electro- and magnetencephalographic responses revealed that the speed-related attentional modulations of activity occurred at an earlier time range (around 240-290 ms), while the coherence-related ones occurred later (around 320-370 ms) post-stimulus. The current results suggest that the attentional selection of motion features modulates neural processing in the lowest-tier regions required to perform the task-critical discrimination.
Asunto(s)
Atención/fisiología , Mapeo Encefálico/métodos , Percepción de Movimiento/fisiología , Red Nerviosa/fisiología , Corteza Visual/fisiología , Adulto , Femenino , Humanos , Masculino , Estadística como Asunto , Adulto JovenRESUMEN
BACKGROUND: In newborns congenital heart defects can take an asymptomatic course, causing a diagnostic gap in the routine examination. Therefore pulsoxymetric screening is under discussion, as it could close this diagnostic gap. PATIENTS AND METHODS: Non-invasive postductal peripheral oxygen saturation assessment was carried out in 3 364 term neonates, 6-36 h of age, in 2008. In asymptomatic neonates with values > or = 95%, no further steps were applied. In those with values between 90% and 94% and no clinical abnormalities, a check-up was carried out 4-6 h later. Echocardiography was performed when the initial value was below 90% or persisted < 95 %. RESULTS: A total of 18 (0.5%) abnormal pulse oximetry values requiring echocardiographic investigation were found in the 3 364 neonates examined. 9 congenital heart defects that had not been recognized prenatally were diagnosed. 4 of these children were also found to have anomalies at the clinical examination. Persistent fetal circulation was noted in 2 of the neonates.In addition neonatal infections has been detected in 7 newborns. 1 neonate with stenosis of the aortic isthmus and 1 with pulmonary stenosis were missed in the screening program, with pulse oximetry saturation levels >95%. These data represent a sensitivity of 82% and a specificity of 99.9%, with a positive predictive value of 50% and a negative predictive value of 99.9%. CONCLUSIONS: Together with the clinical examination, pulse oximetry in neonates is a screening method that has high levels of sensitivity and specificity for early diagnosis of congenital heart defects. The risk-benefit profile may favour pulse oximetry to be standardized and universally used.
Asunto(s)
Cardiopatías Congénitas/diagnóstico , Tamizaje Neonatal , Oximetría , Estudios de Cohortes , Ecocardiografía , Femenino , Alemania , Cardiopatías Congénitas/sangre , Humanos , Recién Nacido , Masculino , Oximetría/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Ultrasonografía PrenatalRESUMEN
BACKGROUND: The serpin squamous cell carcinoma antigen (SCCA, SERPINB3) has been found over-expressed in primary liver cancer and at lower extent in cirrhosis and chronic hepatitis. A novel SCCA-1 variant (SCCA-PD), presenting a single mutation in the reactive centre (Gly351Ala), has been recently identified (rs3180227). AIM: To explore SCCA-1 polymorphism in patients with HCV infection as single etiologic factor and different extent of liver disease. METHODS: One hundred and fourty-eight patients with chronic HCV infection (45 chronic hepatitis, 53 cirrhosis, 50 HCC) and 50 controls were evaluated. SCCA-1 polymorphism was studied by restriction fragment length polymorphism and confirmed randomly by direct sequencing. Circulating SCCA-IgM complex was determined by ELISA. RESULTS: SCCA-PD was detected with higher frequency in cirrhotic patients (45.3%, odds ratio=2.62; 95%CI 1.13-6.10, p=0.038) than in patients with chronic hepatitis or in controls (24.4% and 24%, respectively). Intermediate figures were found in hepatocarcinoma (36.0%). SCCA-IgM in serum was lower in patients carrying SCCA-PD than in wild type patients and the difference was statistically significant in cirrhotic patients (mean+/-S.D.=117.45+/-54.45 U/ml vs. 268.52+/-341.27 U/ml, p=0.026). CONCLUSIONS: The newly identified SCCA-PD variant was more frequently found in liver cirrhosis, suggesting that patients carrying this polymorphism are more prone to develop progressive liver fibrosis.
Asunto(s)
Antígenos de Neoplasias/genética , Hepatopatías/genética , Polimorfismo de Longitud del Fragmento de Restricción , Serpinas/genética , Adulto , Antígenos de Neoplasias/inmunología , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Serpinas/inmunologíaRESUMEN
BACKGROUND: Abdominal ultrasound can detect non-invasively the presence of abdominal portal-systemic collaterals in patients with liver cirrhosis. Abdominal portal-systemic collaterals may be protective from the formation and growth of oesophageal varices, but available data are inconclusive. AIM: We aimed at investigating the relationship between abdominal portal-systemic collaterals and variceal formation and growth. METHODS: We studied 126 cirrhotic patients without (n=43) or with small (n=83) oesophageal varices who entered a protocol of serial ultrasonographic and endoscopic examinations for a median of 55 months. Presence and kind of abdominal portal-systemic collaterals was recorded on first ultrasonography and on each control thereafter. RESULTS: At inclusion, abdominal portal-systemic collaterals were found in 19/43 patients without varices and in 23/83 patients with small varices (NS). There was no difference in variceal formation and growth between patients with and without abdominal portal-systemic collaterals at inclusion. However, patients developing new abdominal portal-systemic collaterals during follow-up had a significantly higher rate of variceal formation (56.2% vs. 22.2%; p=0.024) and growth (52.9% vs. 30.6%; p=0.041) compared with patients with unchanged ultrasonography. CONCLUSIONS: Abdominal collaterals are not protective from the formation or growth of oesophageal varices. Conversely, new abdominal portal-systemic collaterals emergence is a non-invasive clue of formation and progression of varices. Therefore, endoscopy is probably indicated whenever new abdominal portal-systemic collaterals are detected in cirrhotic patients.
Asunto(s)
Circulación Colateral/fisiología , Esófago/irrigación sanguínea , Hipertensión Portal/fisiopatología , Sistema Porta/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Abdomen , Velocidad del Flujo Sanguíneo , Progresión de la Enfermedad , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Sistema Porta/fisiopatología , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis. AIMS: To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality. METHODS: A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day). RESULTS: Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%. CONCLUSIONS: Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.
Asunto(s)
Antibacterianos/administración & dosificación , Ceftazidima/administración & dosificación , Ciprofloxacina/administración & dosificación , Síndrome Hepatorrenal/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Peritonitis/tratamiento farmacológico , Administración Oral , Albúminas/uso terapéutico , Antihipertensivos/uso terapéutico , Femenino , Costos de la Atención en Salud , Síndrome Hepatorrenal/mortalidad , Humanos , Infusiones Intravenosas , Tiempo de Internación , Lipresina/análogos & derivados , Lipresina/uso terapéutico , Masculino , Persona de Mediana Edad , Peritonitis/economía , TerlipresinaRESUMEN
BACKGROUND AND AIMS: Haeme oxygenase could play a role in the pathogenesis of arterial vasodilation in cirrhosis. The aim of this study was to verify the role of haeme oxygenase in the hyporesponsiveness to phenylephrine of small mesenteric arteries in rats with CCl(4) induced cirrhosis, with and without ascites. METHODS: Pressurised small resistance mesenteric arteries were challenged with increasing doses of phenylephrine. Dose-response curves were evaluated under basal conditions, after inhibition of haeme oxygenase with chromium-mesoporphyrin, after inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine-methyl-ester (L-NAME), and then after inhibition of both NOS and haeme oxygenase. Haeme oxygenase protein expression was also analysed. RESULTS: Twenty six control rats and 35 rats with cirrhosis (17 with and 18 without ascites) were studied. Response to phenylephrine was lower in non-ascitic and ascitic cirrhosis than in controls. Chromium-mesoporphyrin increased the response to phenylephrine only in ascitic cirrhosis (p<0.001). L-NAME increased the response to phenylephrine in controls (p<0.001) and in ascitic and non-ascitic cirrhosis (p = 0.002, p<0.001, respectively) but the final response in non-ascitic cirrhosis was similar to that of control rats while it remained impaired in ascitic cirrhosis. Addition of chromium-mesoporphyrin to L-NAME improved the response to phenylephrine in ascitic cirrhosis (p<0.01), with final values not different from those of the other two groups. Protein expression of the inducible isoform of haeme oxygenase was increased in the mesenteric vessels of cirrhotic rats. CONCLUSION: Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of experimental cirrhosis with ascites. NOS plays a major role only in the first stage of the disease.
Asunto(s)
Hemo Oxigenasa (Desciclizante)/fisiología , Cirrosis Hepática Experimental/fisiopatología , Arterias Mesentéricas/fisiopatología , Fenilefrina/farmacología , Vasoconstrictores/farmacología , Animales , Ascitis/fisiopatología , Western Blotting , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Masculino , Arterias Mesentéricas/efectos de los fármacos , Mesoporfirinas/farmacología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/fisiología , Ratas , Ratas Endogámicas WKY , Técnicas de Cultivo de Tejidos , Vasoconstricción/efectos de los fármacosRESUMEN
BACKGROUND: The acute effects of beta-blockers may be different from chronic; mechanisms underlying this difference are poorly elucidated. AIM: To assess portal pressure and its pathophysiological determinants after acute and chronic administration of nadolol. METHODS: In 24 patients with cirrhosis and portal hypertension hepatic venous pressure gradient, portal blood flow and resistance to portal blood flow were measured before, 60-90 min after acute administration of nadolol, and after 1 month. Patients were good-responders if hepatic venous pressure gradient was < or =12 mmHg, or decreased by at least 20%. RESULTS: Eleven and 13 patients were good- and poor-responders to acute administration, respectively. Acute poor-responders showed a lower decrease in portal blood flow (P = 0.04) and a less evident decrease in mean arterial pressure (P < 0.001). Eleven and 13 patients were good- and poor-responders to chronic administration, respectively. Chronic poor-responders showed a larger increase in resistance to portal blood flow compared with good-responders (P = 0.01). Disagreement between acute and chronic effects was seen in 12 patients: six were acute good-responders chronic poor-responders and six were acute poor-responders chronic good-responders. Acute good-responders chronic poor-responders patients had the smallest decreases in portal blood flow and in mean arterial pressure after acute administration, while acute poor-responders chronic good-responders showed the largest (P = 0.05 and 0.01). CONCLUSIONS: Disagreement between acute and chronic effects of nadolol on hepatic venous pressure gradient is common. The mechanism responsible is complex, the acute effect being mainly modulated by arterial hypotension and the chronic effect by changes in portal resistance.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Antihipertensivos/uso terapéutico , Hemodinámica/efectos de los fármacos , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Nadolol/uso terapéutico , Enfermedad Aguda , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Enfermedad Crónica , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Cirrosis Hepática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: The relationships between the levels of portal hypertension and the morphologic alterations of gastric mucosa in patients with liver cirrhosis--generally described as portal hypertensive gastropathy--are poorly defined. PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were examined by endoscopy and measurement of portal hypertension by hepatic venous pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49 cases; six patients showed gastric antral vascular ectasia always associated with gastric lesions described as severe portal hypertensive gastropathy with different localizations. Hepatic venous pressure gradient showed severe portal hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04) than in those with isolated lesions in body-fundus. No relationship was found between hepatic function, as assessed by the Child-Pugh score, and portal hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity of portal hypertensive gastropathy is related to portal hypertension, but portal hypertension is not the sole determinant of the occurrence of endoscopic abnormalities of gastric mucosa. The derangement of liver function does not appear to play any role in the occurrence of portal hypertensive gastropathy.
Asunto(s)
Ectasia Vascular Antral Gástrica/fisiopatología , Hipertensión Portal/fisiopatología , Cirrosis Hepática/fisiopatología , Gastropatías/fisiopatología , Endoscopía del Sistema Digestivo , Mucosa Gástrica/patología , Venas Hepáticas/fisiopatología , Humanos , Persona de Mediana Edad , Presión Venosa/fisiologíaRESUMEN
BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.
Asunto(s)
Endoscopía , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/cirugía , Cirrosis Hepática/complicaciones , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/efectos adversos , Adulto , Anciano , Várices Esofágicas y Gástricas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Dinitrato de Isosorbide/administración & dosificación , Dinitrato de Isosorbide/efectos adversos , Dinitrato de Isosorbide/análogos & derivados , Ligadura , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Propranolol/administración & dosificación , Propranolol/efectos adversos , Prevención Secundaria , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversos , Presión VenosaRESUMEN
The possible relationships between splenomegaly and portal hypertension have been analysed in patients with cirrhosis. In this condition, splenomegaly is not only caused by portal congestion, but it is mainly due to tissue hyperplasia and fibrosis. The increase in spleen size is followed by an increase in splenic blood flow, which participates in portal hypertension actively congesting the portal system.
Asunto(s)
Hipertensión Portal/complicaciones , Cirrosis Hepática/complicaciones , Bazo/irrigación sanguínea , Bazo/metabolismo , Esplenomegalia/etiología , Endotelinas/biosíntesis , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Circulación Hepática , Cirrosis Hepática/fisiopatología , Flujo Sanguíneo Regional , Esplenectomía , Esplenomegalia/metabolismo , Esplenomegalia/fisiopatología , Esplenomegalia/cirugíaRESUMEN
BACKGROUND: Physical restraint rates can be reduced safely in long term care settings, but the strategies used to prevent wandering, falls, and patient aggression have not been tested for their effectiveness in preventing therapy disruption. A restraint reduction program (RRP) consisting of four core components (administrative, educational, consultative, and feedback) was implemented in 1998-1999 in 14 units at two acute care hospitals in geographically distant cities. METHODS: The RRP was targeted at units with prevalence rates of > or = 4% for non-intensive care units (non-ICUs) and > or = 25% for ICUs, as well as two additional units. The RRP was implemented by an interdisciplinary team consisting of geriatricians and nurse specialists. RESULTS: Of the 16,605 admissions to the RRP units, 2,772 cases received RRP consultations. Only six units (four of seven general units and two of six ICUs) demonstrated a relative reduction of > or = 20% in the physical restraint use rate. No increase in secondary outcomes of patient falls and therapy disruptions (patient-initiated discontinuation or dislodgment of therapeutic devices) occurred, injury rates were low, and no deaths occurred as a direct result of either a fall or therapy disruption event. DISCUSSION: Given the minimal success in the ICU settings, further studies are needed to determine effective nonrestraint strategies for critical care patients. ICU clinicians need to be persuaded of the favorable risk-to-benefit ratio of alternatives to physical restraint before they will change their practice patterns. SUMMARY: Efforts to identify more effective interventions that match patient needs and to identify non-clinician factors that affect physical restraint use are needed.