A direct neural measure of variable precision representations in visual working memory.

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.

[Teledermoscopy by mobile phones : Reliable help in the diagnosis of skin lesions?] / Teledermatoskopie mittels Smartphone : Zuverlässige Hilfe bei der Diagnostik von Hautläsionen?

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.

Neural correlates of multiple object tracking strategies.

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.

HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients.

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.

Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine.

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.

Distinct neural correlates of attending speed vs. coherence of motion.

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.

Implication of pulse oxymetry screening for detection of congenital heart defects.

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.

New abdominal collaterals at ultrasound: a clue of progression of portal hypertension.

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.

Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost.

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.

Metabolic control of kidney hemodynamics in normal and insulin-dependent diabetic subjects. Effects of acetoacetic, lactic, and acetic acids.

Diabetes mellitus is associated with important changes in renal hemodynamics. The purpose of this study was to determine whether an increase in blood concentration patterns of ketone bodies and lactic acid, organic acids often elevated in poorly controlled insulin-dependent diabetes mellitus (IDDM), could contribute to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) regardless of changes in circulating levels of glucose and insulin. Six IDDM patients and six normal subjects were given a saline infusion (15 mumol.min-1.kg-1) for 2 h, an acetoacetic acid infusion (15 mumol.min-1.kg-1) for another 2 h, and then a saline infusion after an overnight fast during euglycemic insulin-glucose clamp. Acetoacetic acid infusion resulted in an increase of blood ketone bodies in the range of 0.7-1.5 mM from a basal value of 0.1-0.3 mM. GFR was 125 +/- 16 and 136 +/- 17 ml.min-1.1.73 m-2 in normal and IDDM subjects, respectively, during baseline saline infusion and 138 +/- 21 (P less than .01 vs. basal level) and 158 +/- 15 ml.min-1.1.73 m-2 (P less than .001 vs. basal level) during acetoacetic acid infusion. During the last saline infusion, renal hemodynamic patterns decreased again to baseline levels. Another six IDDM patients and six normal subjects were given saline, lactic acid, and saline infusions at the same rates of infusion after an overnight fast during euglycemic insulin-glucose clamp. Lactic acid concentration increased from approximately 0.5-0.8 to 1.0-1.5 mM in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Disagreement between acute and chronic haemodynamic effects of nadolol in cirrhosis: a pathophysiological interpretation.

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.

Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial.

Sublingual captopril (25 mg) was compared with sublingual nifedipine (10 mg) to determine their effectiveness and safety in the treatment of hypertensive emergencies. In nine of 10 patients who received sublingual captopril, mean (+/- SD) systolic blood pressure and diastolic blood pressure dropped from 245 +/- 39 to 190 +/- 25 mm Hg (P less than .0025) and from 144 +/- 8 to 115 +/- 8 mm Hg (P less than .001) at 50 minutes, respectively. The hypotensive effect of the drug was maintained for a mean of 4 hours. In six of nine responders to sublingual captopril, blood pressure-lowering effect was associated with a clear improvement of end-organ failure within 60 minutes. There were no side effects, including a dangerous fall in blood pressure or reflex tachycardia. Sublingual nifedipine lowered diastolic blood pressure and systolic blood pressure in eight of 10 patients. The hypotensive effect of nifedipine was more rapid than that of captopril (10 vs 20 minutes for diastolic blood pressure and 20 vs 30 minutes for systolic blood pressure, respectively), but no difference was observed in the time or in the magnitude of peak hypotensive effect between the two treatments, nor was a difference observed in the duration of hypotensive effect. In six of eight responders to nifedipine therapy, a clear improvement of symptoms and signs of end-organ failure was observed within 60 minutes. In three patients, minor side effects were observed. We conclude that sublingual captopril effectively and safely lowers arterial blood pressure in patients with hypertensive emergencies.

Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis.

BACKGROUND: Several studies carried out in a limited number of patients demonstrated a wide range of overestimation of glomerular filtration rate (GFR) by serum creatinine level and creatinine clearance (Ccr) in liver disease. METHODS: We simultaneously evaluated Ccr, inulin clearance, and predicted GFR calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance was considered the gold standard for GFR evaluation. RESULTS: The sensitivity of serum creatinine level, predicted GFR, and Ccr in detecting renal failure was 18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per 1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19 mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate markers of GFR in group 1 patients, while both overestimated GFR by about 50% in group 2 patients. An increased tubular secretion of creatinine accounted for the disparity between Ccr and inulin clearance in these patients. CONCLUSIONS: Our results indicate that renal failure is greatly underestimated on the basis of serum creatinine level and Ccr in cirrhotic patients. Clinical implications of this observation include excessive dosage of potentially nephrotoxic drugs and failure to recognize renal impairment induced by such medical treatments as diuretic therapy or paracentesis.

The self-morningness/eveningness (Self-ME): An extremely concise and totally subjective assessment of diurnal preference.

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.

Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach.

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.

Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow.

Splanchnic arteriovenous differences for several intermediary metabolites of carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in seven normal subjects, eight patients with cirrhosis, and six patients with cirrhosis after surgical portosystemic shunt ( SPSS ) after an overnight fast. Arteriovenous differences in the legs were also determined together with flux measurement. The individual turnover rates of acetoacetate (AcAc) and 3 hydroxybutyrate (beta OHB) were also determined by means of isotopic techniques. Splanchnic gluconeogenic precursors and FFA uptakes were lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.05 and P less than 0.01, respectively). Splanchnic triglyceride output was also lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.01), whereas no significant differences were found for AcAc, beta OHB, and glucose release. In the group of cirrhotic patients without SPSS , those patients with negligible signs of portal systemic shunt and normal splanchnic blood flow had uptake of gluconeogenic precursors and of FFA normal or higher than that of normal subjects, whereas those patients with signs of spontaneous portal systemic shunt behaved like cirrhotic patients with SPSS . Alanine release from the leg was lower in both cirrhotic patient groups. Tracer determined hepatic output of AcAc and beta OHB was higher in cirrhotic patients with SPSS (P less than 0.05). Plasma clearance rates of AcAc and beta OHB were significantly elevated in both cirrhotic patient groups. Close agreement was found between tracer and catheterization techniques in the evaluation of ketone body production in cirrhotic patients with SPSS , whereas in cirrhotic patients without SPSS tracer determined hepatic output was slightly lower, possibly because of extrahepatic splanchnic tissue ketone body uptake. In conclusion, our data in patients with cirrhosis indicate that: 1) splanchnic uptake of gluconeogenic precursors and of FFA was related to the degree of portal systemic shunt, e.g. to the degree of effective hepatic blood flow; 2) liver triglyceride but not ketone body output was decreased by the impaired FFA (and glycerol) liver uptake; 3) the higher circulating levels of gluconeogenic precursors (except alanine) and of FFA appeared at least partially due to lower hepatic removal of these metabolites; and 4) peripheral use of ketone bodies was increased and alanine release from the leg reduced in patients with cirrhosis.

Effects of iloprost, a prostacyclin analog derivative, on renal plasma flow, renal function, and renin-aldosterone system in humans.

The effects of iloprost, a stable analog derivative of prostacyclin, on heart rate, blood pressure, renal plasma flow (RPF), glomerular filtration rate, filtration fraction, urine flow, fractional excretion of sodium (FENa), proximal fractional sodium reabsorption (PFRNa), fractional sodium resorption at the ascending limb of Henle's loop (HFRNa), plasma renin activity (PRA), and plasma aldosterone concentration (PA) were evaluated in patients with peripheral vascular disease and normal renal function. In 10 patients the drug was administered intravenously for 6 hours daily for 6 days at a rate of 1 ng/kg/min. In 7 patients iloprost was also administered at a dose of 2 ng/kg/min for the same time. There was no significant change in heart rate and blood pressure at both iloprost doses. At the dose of 1 ng/kg/min the drug had no effect on renal hemodynamics and function, PRA, and PA. At the dose of 2 ng/kg/min iloprost significantly increased RPF (p less than 0.025) and FENa (p less than 0.025) and significantly decreased HFRNa (p less than 0.025) without affecting glomerular filtration rate, filtration fraction, urine flow, PFRNa, PRA, and PA. No correlation was found between the increase in RPF and FENa (r = 0.01). We conclude that at a dose of 2 ng/kg/min, but not 1 ng/kg/min, iloprost has a natriuretic effect secondary to inhibition of sodium reabsorption at the ascending limb of the Henle's loop and not related to the renal hemodynamic effect.

Malnutrition in alcoholic and virus-related cirrhosis.

The study aimed to define the prevalence, characteristics, and clinical importance of nutritional disorders in patients with liver cirrhosis. Nutritional status was evaluated in 120 hospitalized patients--77 with alcoholic and 43 with virus-related cirrhosis--by anthropometric, visceral, and immunologic measurements. Energy malnutrition, defined as triceps skinfold thickness (TSF) and/or midarm muscle circumference (MAMC) below the 5th percentile of standard values, was found in 34% of the study population. Patients below the 5th percentile for MAMC and/or TSF showed significantly lower survival rates at e, 6, 12, and 24 mo compared with patients above the 5th percentile. Protein malnutrition (low albumin, transthyretin, transferrin, and retinol-binding-protein concentrations) and immunoincompetence (abnormal response to skin tests) were much more frequent (81% and 59%) than energy malnutrition (34%). Serum proteins correlated with the degree of liver function impairment, but not with immunologic tests. The prevalence, characteristics, and severity of protein-energy malnutrition were comparable in alcoholic and viral cirrhosis. Malnutrition was correlated with the clinical severity of the liver disease. The study shows that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appear to be related to the degree of liver injury rather than to its etiology. Compared with other methods, which have important limitations in liver disease, anthropometry is currently the most reliable method for nutritional assessment in clinical practice and may be valuable for predicting survival in cirrhotic patients.

Vitamin E and necrotizing enterocolitis.

Although vitamin E has been shown to reduce the incidence of severe sequelae from retrolental fibroplasia, there have been recent suggestions that its use may be associated with an increased incidence of necrotizing enterocolitis (NEC). A review was made of experience with vitamin E, both intramuscular and oral, and NEC over a 4 1/2-year period. Of 418 infants of birth weight less than 1,500 g admitted during this period, 28/209 infants who had received vitamin E had definite NEC (13.4%) compared with 12/209 who had not received vitamin E (5.74%, chi 2 = 7.07, P = .008). For infants of birth weight less than 1,250 g, 16/103 infants who received vitamin E developed NEC v 1/159 who had not (chi 2 = 21.1, P less than .001); the incidence of NEC was not significantly different between the two groups for infants with birth weight between 1,250 to 1,500 g. The early mortality (less than seven days) for infants with birth weight of 1,500 g or less was significantly greater for those who had not received vitamin E (43.5% v 13.8%, chi 2 = 44.9, P less than .001), most probably a reflection of the omission of this drug for the most critically ill infants in this retrospective review. The incidence of NEC was not different for infants with birth weight of 1,500 g or less who received intramuscular vitamin E compared with control infants from the same period. For those infants for whom serum tocopherol levels were available, no infant who developed NEC and who had received only oral vitamin E had a serum tocopherol levels of greater than 3.5 mg/100 mL.(ABSTRACT TRUNCATED AT 250 WORDS)