Preventive-comprehensive assessment (PCA): a new screening method for subclinical cognitive problems.

Physicians often need to be able to assess cognition in a simple way, particularly for screening of subclinical processes in aged people. This paper describes a new, quick test battery called preventive-comprehensive assessment (PCA). It consists of six various testing items (repetition of three words, back-spelling of the word "sport", problem searching ina complex picture, recall of the three words, three progressive colored matrices, clock drawing test), evaluating language, recent memory, executive function, judgment and thinking capacities. The total scores. compared to the normal performance of different age groups, allow us to distinguish between normal and pathological status. If abnormal results are recorded, we need to perform further and deeper neuropsychological investigations, in order to obtain the possibly exact diagnosis. The PCA battery is sensitive and reliable; it can be used in itself, or as a part of a more complex battery of an intense comprehensive evaluation (ICE), carried out in population screening aimed at promoting healthy and active aging.

Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.

BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?

Hepatocellular carcinoma (HCC) generally occurs in patients with cirrhosis. Curative options, such as liver transplantation, hepatic resection, and percutaneous alcohol injection, are applicable to a minority of cases. Because systemic chemotherapy and radiation therapy provide dismal results, transarterial chemoembolization (TACE) remains the sole approach to antagonizing the cancer growth in most patients. Although most tumors show an extensive necrosis after TACE, the beneficial effect on survival has not been properly substantiated, so that its application still remains a matter of debate. This review analyzes the results of randomized clinical trials on TACE. In most studies, TACE did not increase the survival of patients as compared with the palliative treatment. However, several methodologic and technical pitfalls may have adversely affected the results of these trials, such as inadequate patient selection and statistical power of the study design, a nonoptimal procedure, and treatment repetition not tailored to the cancer response and patient tolerance. Nonetheless, the literature will hardly be enriched by new trials including untreated patients because, wrong or right, TACE is currently considered the standard treatment of unresectable HCC. It seems more realistic to expect randomized studies comparing different techniques and time schedules of treatment, as well as TACE alone versus combined procedures.

Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis.

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites.

Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P =.021), lower indicized peripheral vascular resistance (P =.013), and increased CI (P =.004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r = 0.53; P =.002) and CI (r = 0.45; P =. 016), and inversely correlated with peripheral vascular resistance (r = 0.46; P =.013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis.

Ageing affects anoxia/reoxygenation injury in rat hepatocytes.

BACKGROUND: The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation. METHODS: Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release. RESULTS: During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats. CONCLUSIONS: The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Chemiluminescent real time imaging of post-ischemic oxygen free radicals formation in livers isolated from young and old rats.

Oxygen free radicals generation is a major cause of liver injury during reperfusion. Luminescence analysis has been recently proposed to measure free radical generation by isolated cells or organs, but it allows only global tissue luminescence. Using a special Saticon videocamera with image intensifier we aimed to visualize and localize oxygen free radical generation in isolated perfused livers exposed to an oxydative stress. Livers isolated from rats aged 4 and 30 months were exposed to ischemia/reperfusion; photons emission by the organs was continuously recorded. Lucigenin was utilized as a chemiluminigenic probe to assess superoxide anion generation. In both groups, chemiluminescence was not detectable during ischemia, while it was observed after reperfusion. Photons emission started after few minutes of reperfusion, was maximal after 15-20 min and disappeared within 50-60 min. Chemiluminescence emitted by livers from younger rats however, was significantly higher when compared to chemiluminescence emitted by organs isolated from old rats (0.8 +/- 0.1 vs 0.44 +/- 0.08 photons x 10(5)/s, respectively, after 15 min; p < .01). The superimposition of chemiluminescent and live image permitted to determine the regional production rate and distribution of photons. In conclusion, the age of the rats influences significantly the amount of oxyradicals produced in the liver during post-ischemic reperfusion. The method described, allowing the visualization in real time of oxygen free radicals generation on the surface of isolated intact organs, represents a novel and potent tool for the study of oxidative stress.

Effect of ischemia--reperfusion on heat shock protein 70 and 90 gene expression in rat liver: relation to nutritional status.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.

BACKGROUND/AIMS: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis. METHODS: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period. RESULTS: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups. CONCLUSIONS: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Intermittent anoxia reduces oxygen free radicals formation during reoxygenation in rat hepatocytes.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

Liver transplantation in Italy: preliminary 10-year report. The Monotematica Aisf-Olt Study Group.

Experience in liver transplantation (OLT) in Italy over a ten-year period is reported. Data were obtained using a multiple-items form collected from Italian liver transplant centres (reference centres) and other Italian institutions actively involved both in the processes of evaluation of the candidates and the follow-up of liver transplant recipients (afference centres). During this period, a total of 1046 liver transplants were performed on 954 patients, with a cumulative proportional survival of 71%. The most common indication for liver transplantation was post-hepatitic cirrhosis due to either hepatitis B virus (+/-hepatitis Delta virus) or hepatitis C virus infection. Good survival rates were observed, particularly in controversial indications, such as alcoholic cirrhosis, post-hepatitic hepatitis B virus-related cirrhosis and hepatocellular carcinoma, most likely due to proper and careful selection of the patients. Cirrhosis, secondary to an autoimmunity-based liver disease, showed the highest rate of rejection episodes. Infections, in our study population, were the most common cause of death after transplantation.

High plasma levels of atrial natriuretic peptide in preascitic cirrhosis: indirect evidence of reduced natriuretic effectiveness of the peptide.

Controversial results come from spot measurements of plasma atrial natriuretic peptide (ANP) in compensated cirrhotic patients. Moreover, either blunted or exaggerated natriuresis has been described after maneuvers increasing plasma ANP. This does not make it possible to delineate the ANP effectiveness. Plasma ANP, renin activity (PRA) and aldosterone and hematocrit were serially measured (7 AM, 9 AM, 6 PM, and 11 PM) in nine preascitic cirrhotic outpatients and in nine healthy subjects on normal sodium diet (150 mmol/day) and carrying on their usual activities (mobile from 7 AM to 10 PM). Daily natriuresis was monitored the day before and during the study. In both groups, ANP peaked at the end of the recumbence period (7 AM) and declined on the assumption of the upright position, so that both ANP values of the standing period were significantly lower than the mean daily level. These fluctuations were reciprocal to PRA and hematocrit changes. Patients showed steadily elevated plasma ANP and reduced PRA (ANP mean daily level: 33.3 +/- 3.8 vs. 15.5 +/- 3.2 pg/mL, P = .004; PRA: 0.76 +/- 0.23 vs. 1.66 +/- 0.21 ng/mL/hr, P = .003). Aldosterone fluctuations and mean daily level were similar in the two groups (mean daily level: 122 +/- 11 vs. 119 +/- 9 pg/mL). Natriuresis was well adapted to the sodium intake and similar in healthy subjects (day 1: 152 +/- 11 mmol; day 2: 138 +/- 12.5 mmol) and patients (143 +/- 15 mmol; 148 +/- 29 mmol). Preascitic cirrhotic patients on a normal salt intake and carrying on their usual activities develop a new steady state requiring increased ANP levels to maintain a sodium balance.(ABSTRACT TRUNCATED AT 250 WORDS)