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Objectives: Noninvasive evaluation of fibrosis is an on-going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging., Design: We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients., Results: Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score2) fibrosis: BMI (24+/-2 vs. 26+/-2, P=0.0007), AST (56+/-36 vs. 88+/-65, P=0.0159), ALT (92+/-54 vs. 139+/-108, P=0.0290), PLT (220+/-64 vs. 173+/-61, P=0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133+/-786 vs. 1540+/-681, P=0.0003), AST/platelet count ratio index (APRI) (0.80+/-0.87 vs. 1.51+/-1.47, P=0.0010), ABT%d/h30 min (10.8+/-4.5 vs. 7.6+/-3.8, P=0.0007), ABT%d/cum120 min (8.9+/-3.3 vs. 6.5+/-3.1, P=0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: -0.569+(BMIx0.107)+(APRIx0.169)-(PLT/SPDx0.304), and Model 2: 2.376+( APRIx0.152)-(ABTd/h30x0.043)-(PLT/SPDx0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score., Conclusion: These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.

Background: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3-DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched artificial feeding., Design: The present study was carried out to test the hypothesis that a possible increase in 2,3-DPG concentration can also be obtained in human neonates who are fed nucleotide-enriched formula. Preterm neonates born or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa University, with a gestational age >30 weeks and <37 weeks were enrolled in our randomized trial. Recruitment took place within 48-72 hours from birth. Only newborns of mothers deciding not to breast-feed were eligible to be randomized for the supplemented group (FN) or non-supplemented group (RF). Breast-fed newborns were considered the control group (C). The study window (for supplementation and blood samples) was restricted to the first two weeks following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of our study, only 21 neonates were eligible for statistical analysis., Results: The stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be demonstrated; increases in 2,3-DPG concentration that were observed in newborns fed with nucleotide supplemented formula (FN) were comparable to those observed in newborns fed with regular formula (RF) and breast-fed newborns., Conclusions: The EC recommendation for the amount of nucleotides allowed in formula milk does not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether this possible 'pharmacological' effect can be achieved by a higher intake of ingested nucleotides and/or a change in the proportions of single nucleotides contained in milk formulas remain interesting end points to be elucidated.

Objective: The aim of this study was to assess the diagnostic value and the usefulness of sonohysterography (SHG) in the detection of uterine anomalies, compared with other diagnostic methods., Study Design: From January 2002 to December 2003, we collected 54 patients with a history of primary or secondary infertility or repeated spontaneous abortion and with a clinically or sonographically suspected abnormal uterus. All patients had previously undergone hysterosalpingography (ISG). All patients were examined by standard transvaginal ultrasound. Sonohysterography was then carried out by the intrauterine injection of an isotonic saline solution. Suspected uterine anomalies were also confirmed by hysteroscopy (HS) and/or laparoscopy., Results: Sonohysterography was able to detect all the anomalies. The sensitivity and specificity of sonohysterography were the same as for hysteroscopy. However, there was no significant difference between the diagnostic capabilities of the methods analyzed., Conclusions: Transvaginal sonohysterography with saline solution is a low-cost, easy, and helpful examination method for uterine malformations. We propose that sonohysterography should be performed for the primary investigation of infertility and repeated miscarriages.

Purpose: The aim of the present work was to ascertain, through the administration of a psychosocial questionnaire, the difficulties that subjects with defective colour vision experience in carrying out everyday tasks and work, including driving a car with a driver's licence held for no more than 3 years., Methods: Subjects with defective colour vision (n = 151) and subjects with normal vision (n = 302) completed a psychosocial questionnaire regarding the difficulties associated with congenital colour vision deficiency in daily life, work and driving a car. Subjects were diagnosed as colour-blind using the Ishihara test., Results: Statistically significant differences between the two samples were found for daily life activities. Subjects with defective colour vision preferred daytime driving. At night, subjects with defective colour vision had difficulty identifying reflectors on the road and the rear signal lights of cars ahead of them., Conclusion: Colour-blind Calabrian subjects admitted to experiencing colour-related difficulties with a wide range of occupational tasks and leisure pursuits. In particular, colour-blind Calabrian subjects preferred daytime driving, and fewer drove regularly, compared to orthochromatics, who were indifferent to night or daytime driving.

Background: Anti-hepatitis C virus (anti-HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease., Aim: To assess the prevalence and clinical associations of previous (positivity for anti-HBs and/or anti-HBc antibodies) and occult HBV infection (positivity for HBV-DNA by nested-PCR) in the serum of anti-HCV-positive, HCV-RNA-positive, HBsAg-negative patients with various degrees of CLD seen at a tertiary referral centre., Patients: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis)., Results: Forty-eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 +/- 2.7 versus 4.6 +/- 3.0, P = 0.004; staging: 1.6 +/- 1.2 versus 1.0 +/- 1.0, P = 0.01). Eight patients were positive for HBV-DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection-matched HBV-DNA-positive and negative chronic hepatitis patients., Conclusions: Our findings suggest that previous HBV infection among anti-HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.

The optimal concentration of a human placental polydeoxyribonucleotide (PDRN) preparation (100 microg/ml) enhances the growth of human corneal fibroblasts in primary culture depending upon the donor age. In particular, this effect is very consistently reproducible with donors over 60 years of age (p = 0.0028), suggesting a selective benefit of PDRN in the tissue culture of senescent cells. Moreover, this drug may promote the development of human iris pigment epithelium (IPE) cells with much lower concentrations of fetal bovine serum than those suitable for the culture of IPE. Lastly, the use of a 'gauze disk' on the pieces of the corneal explants improves the efficiency of growth of the control fibroblast primary cultures.

To highlight the link between colour blindness and school achievement, the Ishihara and Farnsworth tests were administered to 3,565 high school art students (2,545 girls and 1,020 boys). Analysis showed colour defective students were discriminated against in theoretical subject matter, relative to orthochromate students, but not in the art-related subjects. This emphasizes the need to recognize youth with colour defective vision early.

Objectives: To calculate reference ranges for fetal limb measurements obtained by transabdominal ultrasound at 10-14 weeks of gestation., Methods: Six hundred and six normal fetuses were examined transabdominally in a cross-sectional study by a single observer. The crown-rump length of the fetuses ranged from 31 to 78 mm. Measurement of the length of the humerus, ulna, femur, tibia and foot was attempted from the longest section of each structure. To assess intraobserver repeatability, three sets of repeated measurements were obtained in 26 fetuses., Results: An appropriate ultrasound measurement was obtained in a percentage of cases ranging from 93.2% to 97.9%. A significant correlation was found between crown-rump length measurements and humerus length (r = 0.74, P < 0.001), ulna length (r = 0.70, P < 0.001), femur length (r = 0.77, P < 0.001), tibia length (r = 0.69, P < 0.001) and foot length (r = 0.58, P < 0.001). Crown-rump length-specific reference ranges for each measurement were calculated with the method of scaled absolute residuals. The study of intraobserver variability showed coefficients of variation ranging from 7.9 to 10.0% and intraclass correlation coefficients ranging from 0.89 to 0.94., Conclusions: Fetal limb size is strongly correlated with crown-rump length. Despite a significant biological variability of the measurements, the availability of reference ranges could be of help in the early diagnosis of fetal skeletal dysplasias.

Background: We addressed the definition of limits of error of %CD4+ and CD4+ counts (AbsCD4+) typical of laboratories of excellence, as well as the grading of laboratories based on the decision to take these limits as boundaries of unacceptable data., Methods: We studied the 99.9% confidence intervals of the means of 24 human immunodeficiency virus (HIV)+ and HIV- blood samples analyzed by 18 laboratories of the Liguria Region Quality Assessment Program (Liguria Region QALI). Regression equations of lower (L1) and upper (L2) confidence limits over the means of data cleared of unusual results were used to interpolate limits of error for mean values in the tested range., Results: L1 and L2 were symmetric around the mean and a single absolute difference (Abs Res) between the limits and the mean was found. Abs Res significantly increased over mean values (P = 0.0005 for %CD4+, P < 0.0001 for AbsCD4+). Limits were compatible with errors shown with blind replicates. Unacceptable results, outside the limits, accounted for 25% and 30% of %CD4+ and for 18% and 35% AbsCD4+ in the Liguria Region QALI and in the Piemonte Region QA Program, respectively. Limits interpolated over the median showed a similar grading. A comparable fraction of unacceptable data was also found with the method used in the U.K. National External Quality Assessment Scheme (NEQAS) immune monitoring scheme., Conclusions: We propose the general use of these regression equations to determine bounds for unacceptable data in proficiency testing and to identify laboratories of excellence., (Published 2002 Wiley-Liss, Inc.)

Background: Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty., Aims: To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation., Methods: Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients., Results: Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels., Conclusions: Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.

Maternal dietary fatty acids (FFAs) intake and corresponding human milk composition relationships have been assessed throughout the first month of lactation in 34 lactating women consecutively enrolled. All mothers were on their habitual diet. Food records (95 items) were administered to the mothers, six-times during the first month of lactation (1 day after delivery, 4, 7, 14, 21, and 28 days after colostrum appearance) and referred to maternal dietary intake of the day before. Milk collected on day 1 was considered as colostrum, day 4 and 7 samples as transitional milk, and day 14, 21 and 28 samples as mature milk. Five gas chromatographic analyses were performed on each sample. Statistics were made using Friedman's and Pearson's test. Maternal dietary saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were significantly related to the corresponding milk pattern in the phase of transitional milk (P<0.01), while total polyunsaturated (PUFAs) content was significantly related only to the mature milk (P<0.01); in this phase about 42% of the variations occurring in PUFAs milk content can be related to variation of maternal PUFAs dietary intake. The results in the present study provide evidence of the relationships between maternal diet and milk composition. The degree of correlation between maternal diet and PUFAs milk content increases throughout milk maturational process and reaches significance only in mature milk. This would imply that advancing lactation, milk PUFAs provision sources gradually shift from adipose tissue catabolism to maternal diet., (Copyright 2001 Harcourt Publishers Ltd.)

Objective: Liver biopsy is mandatory for correctly grading and staging chronic hepatitis activity. Nevertheless, serum markers of fibrogenesis may be useful to help us understand the mechanisms of the fibrogenic process, to follow-up patients, and to establish the efficacy of therapy. In this study, our aim was to identify the relationships between pro-collagen III peptide (PIIIP) serum levels and detailed liver histology in a group of untreated patients with chronic hepatitis C (CHC)., Methods: We studied 147 CHC patients. Correlation analysis of PIIIP serum levels was performed in 109 patients, after having excluded those with alcohol abuse or concomitant hepatitis B virus infection. PIIIP serum levels were assessed using an assay that measures both Col 1-3 peptide (reflecting collagen synthesis) and Col 1 peptide (reflecting collagen degradation). Relationships of serum PIIIP with histology was carried out by evaluating grading and staging separately. Moreover, each component of the necro-inflammatory score was also taken into consideration., Results: PIIIP levels were abnormal in 101 patients (93%). Moreover, PIIIP levels were no different between patients with (12.1 +/- 6.3 ng/ml) or without (13 +/- 5.8 ng/ml) fibrosis. In univariate analysis, no relationship was observed with fibrosis (rs = 0.033, not significant), while PIIIP levels were significantly correlated with lobular necrosis only (rs = 0.295, P = 0.0020). Multivariate analysis confirmed this latter finding (P = 0.0150). Among biochemical parameters, PIIIP showed relationships with aminotransferase (AST, rS = 0.294, P = 0.0022; ALT, rs = 0.236, P = 0.0142) and alkaline phosphatase (rs = 0.146, P = 0.0223)., Conclusions: In patients with CHC, serum PIIIP levels reflect histological parameters strictly related to fibrogenesis. Therefore, PIIIP is a useful tool to evaluate ongoing fibrogenic activity of CHC. A complete histological score is needed in order to understand the relationships between biochemical markers of fibrogenesis and histology.

Objective: The presence of steatosis is a common histological finding in patients with chronic hepatitis C (CHC). The causes of the severity of this condition are not yet clear, although both metabolic and viral factors supposedly are involved. In this study our aim was to examine the possible influence that leptin levels, hepatitis C virus (HCV) RNA levels, and hepatitis G virus (HGV) infection have on the severity of steatosis and on the presence and degree of fibrosis in patients with CHC., Methods: One hundred eighty-two CHC patients with histological findings of steatosis were chosen from among a cohort of patients referred to our center for staging of liver disease. Among them 48 CHC patients were accurately selected so as to rule out possible confounding factors for the presence of steatosis (diabetes mellitus, hyperlipemia, obesity, alcohol). Leptin levels, HCV RNA levels, and HCV genotype, and the presence of HGV RNA were assessed in these patients and related to histological findings., Results: We found that leptin levels in CHC patients were similar to those in healthy subjects. No relationship was found between leptin levels and severity of steatosis. HCV RNA levels, HCV genotype, and the presence of HGV infection were no different among CHC patients with various degrees of steatosis. Leptin was not related to different degrees of fibrosis, whereas higher viral load was the only parameter associated to higher fibrosis scores., Conclusions: These findings suggest that the degree of steatosis in patients with CHC does not seem to depend on serum leptin levels or on viral factors, at least as far as HCV viremia and genotype and HGV infection are concerned. The severity of fibrosis does not seem to be influenced by leptin levels, whereas HCV viral load does seem to play some role.

Objective: Proton pump inhibitors and antimicrobial agents are widely used to eradicate Helicobacter pylori (H. pylori) infection. In the general population the prevalence of infection and of polypharmacy increases the possibility of drug-drug interactions during H. pylori eradication therapy. The purpose of the present study was to assess the prevalence, degree, and clinical relevance of metabolic interference with the cytochrome P450 enzymatic system occurring during 1 wk of administration of omeprazole, lansoprazole, or pantoprazole followed by the association of clarithromycin and metronidazole for another week. The 13C aminopyrine breath test (ABT) was chosen to screen for possible interactions., Methods: We studied 30 patients referred to our Unit for H. pylori eradication therapy. They were randomized to receive either omeprazole (20 mg b.i.d.), lansoprazole (30 mg b.i.d.), or pantoprazole (40 mg b.i.d.) for 2 wk. During the second week clarithromycin (250 mg b.i.d.) and metronidazole (500 mg b.i.d.) were added. ABT was performed before, and at the end of the first and second week of therapy. Percentage of the administered dose of 13C recovered per hour at the peak (percent 13C dose/h at the peak) and cumulative percentage of administered dose of 13C recovered over time at 120 min (percent 13C dose cum120) were the ABT evaluated parameters., Results: At baseline all patients showed a normal liver function. In individual patients during treatment we observed various liver metabolic interactions both as inhibition and induction, as well as after the first and the second week of therapy. However, mean modifications of the ABT parameters during the 2 weeks of therapy were not statistically significant compared to baseline values. None of the patients who had ABT variations complained of side effects., Conclusions: H. pylori eradication therapy interferes with cytochrome P450-dependent liver metabolic activity. However, the clinical relevance of these metabolic interactions is not yet apparent, and further investigation is needed. H. pylori eradication therapy appears safe, but these interactions should be considered in the choice of proton pump inhibitor and antimicrobial agents.

Background/aims: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma., Methods: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test., Results: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels., Conclusions: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.

Mean blood flow velocity (MFV) of the middle cerebral arteries was monitored in 19 healthy, adult, right-handed subjects during the resting phase and the execution of a series of neuropsychological tests: two right/left discrimination tasks, two mental rotation paradigms (the Ratcliff's test and a cube comparison test) and a phonemic fluency task, which was utilised as an internal control. In the group as a whole, the Ratcliff's test was associated with a significant bilateral increase in MFV versus both the resting state (right: p < .000001, left: p < .000001) and right/left discrimination tasks (task 1: right: p = .003, left: p = .005; task 2: right: p = .001, left: p = .001). The cube comparison in turn produced a significant increase in MFV versus both the baseline conditions (right: p < .000001, left: p < .000001) and the Ratcliff's test (right: p = .01, left: p = .002). As expected, the fluency task was associated with a significant asymmetric increase in cerebral perfusion (left > right: p = .0001). Increasing task difficulty (right/left discrimination < Ratcliffs test < cube comparison) was paralleled by a roughly proportional rise in MFV values (right: r = .424, p < .01; left: r = .331, p = .01). In conclusion, we were able to demonstrate that (1) in addition to the amount of MFV variation due to right/left discrimination (when required), mental rotation per se causes a bihemispheric activation irrespective of the experimental paradigm; (2) the MFV variation is proportional to the difficulty of the tasks.

Objectives: To study whether determining alpha-glutathione S-transferase (alpha-GST) might improve the assessment of chronic hepatitis C (CHC) patients with near normal alanine aminotransferase levels (NNA)., Design and Methods: We studied 119 viraemic CHC patients. They were subdivided into two groups according to the pattern of alanine aminotransferase (ALT) alteration, i.e. consistently above (HA) or below (NNA) twice the upper normal value. In these patients we assessed alpha-GST and correlated its levels to clinical, histological, and virological findings, further evaluating whether alpha-GST might improve the assessment of CHC patients with NNA., Results: alpha-GST showed a significant correlation with aminotransferases, though not with histological necroinflammatory activity and fibrosis or with hepatitis C virus RNA levels. Twenty-seven patients had NNA (23%), and within this subgroup of patients alpha-GST identified a subset of patients with a higher viral load., Conclusions: alpha-GST in CHC patients is related to hepatocellular necrosis parameters, but unrelated both to histology and to viraemia. However, in patients with NNA, alpha-GST identified a subgroup of patients with a higher viral load. In this subgroup of patients alpha-GST alteration likely represents the expression of a more severe damage. Because this injury is not detectable by the usual biochemical or histological work-up, we suggest that alpha-GST could a useful tool for monitoring liver damage over time.

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.

Background/aims: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters., Methodology: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders., Results: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%., Conclusions: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.

Background: Liver transplantation is nowadays the therapeutic option for end-stage liver disease. Correct disease staging is the main step towards improving the timing of listing for liver transplantation so as to avoid premature or late entry. The need for correct prognostic evaluation is due to the limited number of donors and to the increasing number of patients awaiting transplantation. Our aim was to verify whether Child-Pugh's score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination., Methods: We evaluated 182 cirrhotic patients (44 Child-Pugh class A, 97 class B, and 41 class C) of mixed aetiology referring to a tertiary care centre for functional staging of liver disease. These patients were prospectively followed-up for 12-72 months. During this period, 45 patients died, 46 received a transplant, and 91 survived without transplantation. The end-point of analysis was either survival or liver disease-related death at the 6th, 12th, 18th and 24th months of follow-up. The 46 transplanted patients were excluded from the study upon transplantation., Results: In our study, a cut-off for Child-Pugh's score < 8 confirmed its usefulness, especially in short-term prognostic prediction, while mid- and long-term prediction improved by almost 10% by using the combination of a Child- Pugh's score > 8 and an MEGX value < 15 mg/l. Cox's multi-variate regression analysis indicated that MEGX values either with Child-Pugh's score or with prothrombin activity and ascites were independent prognostic variables., Conclusions: Besides confirming that Child-Pugh's score as the basis of prognostic evaluation of cirrhotic patients, these results suggest that the MEGX test might be a complement to the original score when a patient is being evaluated for a liver transplantation programme.

Background: Hepatitis C virus infection accounts for varying severity of chronic liver disease. Clinical manifestations of infection have been related to different virus genotypes, with conflicting results., Design: We performed a cross-sectional study on a Northern-Italian group of patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma related to hepatitis C virus infection in order to verify the association of different viral strains and the outcomes of viral disease., Methods: Two hundred and seventy-one patients referred to our unit for liver disease were studied and clinical, biochemical, histological, and functional parameters were investigated., Results: Different viral genotypes were not associated with peculiar findings in any of the degrees of liver disease. However, a progressive age increase was associated with disease severity, although clinical and functional staging of cirrhotic patients with hepatocellular carcinoma was better compared to tumour-free cirrhotic patients. There was an increased prevalence of genotype 1b related to the age of the patients. In multivariate regression analysis the patients' age and apparent duration of infection were independently associated with the presence of cirrhosis and only the age of patients was associated to hepatocellular carcinoma., Conclusions: In the population we studied age of the patients seemed to be a determinant conditioning disease severity, likely reflecting older infections and long-standing liver disease. The prevalence of certain genotypes in varying degrees of liver disease could be an epiphenomenon which might also be explained by the changing prevalence of infecting strains over the past decades.

In 1993-94, in Liguria (a northwestern Italian region) a study was carried out on dyschromatopsia, a congenital sex-linked form of colour blindness. 3124 junior high school boys aged 10-15 years were tested using Ishihara plates (1973 edition) and Farnsworth's D-15 test (1947 edition). 152 students were identified as colour blind (4.87%), a value slightly below the Italian average of 5.3%. The school achievement of these students was assessed by means of the school marks of two randomised subsamples composed of 82 dyschromates and 82 orthochromates, paired homogeneously by age and class. Statistical analysis indicated significantly lower general school achievement for the 82 dyschromate subjects (except for art). The learning difficulties of dyschromate persons for whom colour is a basic didactic tool are discussed. Introduction of dyschromatopsia tests at preschool would be desirable.

Background/aims: The aim of this study was to evaluate the relationship between plasma elimination of lidocaine and monoethylglycinexylidide (MEGX) formation, which is considered to be a quantitative liver function test., Methodology: The study included ten healthy subjects and 54 patients: 27 with chronic hepatitis and 27 with cirrhosis. Lidocaine and MEGX were measured at 0, 2, 5, 10, 15, 30 min and then every 30 min for 180 min using the TDX system., Results: In cirrhotic patients, the lidocaine half-life of the slow decline phase of the plasma disappearance curve (beta-HL) and the lidocaine half-life of hepatic elimination from the second compartment (K20-HL) proved to be significantly abnormal, as did all parameters of MEGX formation. In chronic hepatitis, both the lidocaine kinetics and the MEGX formation parameters were within the normal range. In chronic hepatitis patients, MEGX formation (AUC 0-180) was significantly correlated to K20-HL (rs = -0.633, p < 0.001) and to the rapid decline phase of the plasma disappearance curve (alpha-HL, rs = -0.483, p < 0.05). In cirrhotic patients, MEGX was significantly correlated to K20-HL (rs = -0.423, p < 0.05) and to beta-HL (rs = -0.500, p < 0.01)., Conclusions: These results show that in chronic active hepatitis, MEGX formation from lidocaine is maintained as a metabolic process, whereas it is altered in cirrhotic patients. The interrelationship between lidocaine elimination and MEGX formation were somewhat different in the two liver diseases.

Objectives: Monoethylglycinexylidide (MEGX) is the main lidocaine metabolite and its formation depends on liver microsomal activity. MEGX formation was studied in comparison with the histological score of chronic hepatitis and with the clinical score (Child-Pugh) of cirrhosis. Furthermore, we evaluated its ability to distinguish between the two liver diseases., Methods: We studied 284 patients: 130 with chronic hepatitis (on the basis of the histological activity index, 45 had mild chronic hepatitis, 54 had moderate chronic hepatitis, and 31 had chronic hepatitis with cirrhosis) and 154 with cirrhosis (49 Child-Pugh's class A, 78 class B, and 27 class C). MEGX formation was evaluated 15, 30, and 60 min after lidocaine administration., Results: MEGX formation showed a stepwise decline corresponding to worsened liver disease. MEGX values were related both to the histological score in chronic hepatitis and to the clinical score in cirrhosis. Significantly lower values were found in females < 50 yr of age than in males of the same age. The MEGX test showed great efficacy in discriminating between chronic hepatitis and cirrhosis compared with standard liver tests., Conclusions: Measurement of MEGX formation proved to be a safe test, allowing us to show that functional subgroups can be identified both in chronic hepatitis and in cirrhosis. Thus, this test could integrate both the histological grading of chronic hepatitis and the clinical staging of cirrhosis.

The fatty acid composition of breast milk from 20 Italian women, delivering at term and on ad libitum diets, was analyzed with high-resolution gas chromatography. Milk samples were collected twice a day, on the 1st, 4th, 7th, 14th, 21st and 28th day after colostrum appearance. No significant differences were detected between the two daily samples. During the maturation process a significant reduction in long-chain polyunsaturated fatty acids of the n-6 series (p = 0.002) and n-3 series (p = 0.005) was recorded, particularly in arachidonic acid (p = 0.035), docosatetraenoic acid (p = 0.035) and docosahexaenoic acid (p = 0.032). The linoleic acid/n-6 and alpha-linolenic acid/n-3 ratios increased (p = 0.024 and p = 0.037), while the docosatetraenoic/docosahexaenoic acid ratio decreased (p = 0.032). The fatty acid composition of mature milk was the following: saturated 45.50%; unsaturated 54.51%; monounsaturated 42.69%; polyunsaturated 11.82%; long-chain polyunsaturated 1.27%; linoleic acid 9.79%, and alpha-linolenic acid 0.36%. The fatty acid composition of milk collected from Italian women appears similar to that of women in other southern European countries and, therefore, could reflect dietary habits.

Lipoprotein (a) [Lp(a)] concentrations were determined in 365 patients undergoing coronary angiography for stable angina (n = 159), unstable angina (n = 99), recent myocardial infarction (n = 45), and nonischemic heart disease (cardiomyopathy or valvular disease, n = 62, non-IHD). Mean +/- SD and median Lp(a) concentrations in stable angina (29.9 +/- 29.2;22 mg/dl) did not differ from those in non-IHD (26.9 +/- 26.3; 17), but were significantly lower than in patients with unstable angina (52.7 +/- 36.6; 58) and myocardial infarction (44.8 +/- 36.4; 34) (p < 0.01). Coronary angiography revealed that 261 patients, including 4 patients in the non-IHD group, had significant (> or = 50%) coronary lesions. Lp(a) was higher in patients with (41 +/- 35; 32) than in those without (28 +/- 27; 19) angiographic evidence of significant coronary stenosis (p < 0.05) and showed a weak univariate correlation with the angiographic index (Total Score) of the severity of the disease (r = 0.106;p < 0.05). However, in the subgroup of 303 patients with stable/unstable angina or myocardial infarction, Lp(a) was predictive neither of angiographic presence nor of severity of coronary disease. Patients were then ranked according to the Total Score values. Among patients with comparable angiographic severity of coronary artery disease, Lp(a) appeared to be remarkably higher in patients with acute ischemic syndromes (unstable angina, myocardial infarction) than in patients with stable angina. In conclusion, Lp(a) was roughly twice as high in acute (unstable angina, myocardial infarction) than in chronic (stable angina) ischemic syndromes, but there was no difference between chronic stable angina and non-IHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Eighty-one patients with HCV positive chronic active hepatitis (CAH) were studied to correlate, in multivariate regression analysis, liver tests with the histological activity index (HAI). The median HAI value (9.4) divided the patients into two groups; 44 under the 9.4 value (moderate CAH) and 37 above (severe CAH). Multiple regression improved the significance of nine biochemical parameters related to HAI in univariate analysis, and backward stepwise analysis identified the combination of alanine-aminotransferase (ALT), gammaglobulins (gamma GL), gammaglutamyl transpeptidase (gamma GT) and prolyl-hydroxylase (PH) as the best relationship with HAI (R = 0.520, p < 0.0001). A biochemical activity index (BAI) calculated as: 2.304 + ALT x 0.013 + gamma GL x 1.76 + gamma GT x 0.008 + PH x 0.012 showed the higher significant difference between moderate (7.7 +/- 1.3) and severe (12.2 +/- 2) CAH (p < 0.0001). These results suggest that this BAI could be a pointer for checking activity of chronic liver diseases.

We tested the safety and the usefulness of intravenous fibrinolysis in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-hour Holter monitoring (phase 1) despite maximal medical therapy. After fibrinolysis, recurrence of ischemia was recorded during 1 week of observation in CCU including 2 24-hour Holter monitoring at the beginning and at the end of this week (phase 2): 17 patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 patients continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 10 patients underwent CABG or PTCA for refractory angina, 6 other patients with refractory angina continued medical therapy, 1 patient had a myocardial infarction and 2 patients died (p less than 0.001). Phase 1: the duration of total ischemia (min/24 hours) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). Phase 2: in comparison with phase 1, duration of total ischemia was significantly reduced (p less than 0.001). A percent value expressing this variation was calculated for each patient: (min of ischemia in phase 2 - min of ischemia in phase 1/min of ischemia in phase 1). The variation thus obtained again gave information on the clinical outcome: the greater was the reduction, the lower was the risk of cardiac events (p less than 0.001). Our data suggest that: clinical stabilization may be obtained with the addition of fibrinolysis to conventional treatment; Holter monitoring bears prognostic information helpful in identifying patients who need further intervention.

Gas-chromatographic analysis of the fatty acids (P/S ratio) in 10 samples of amniotic fluid and 10 samples of the pellets obtained after centrifugation of amniotic fluid at 3500 X g for 60 minutes were carried out to evaluate the effects of contaminants that might be present in amniotic fluid. The P/S ratio is used as an index of the degree of maturity of the fetal or neonatal lung. We propose a standard procedure of centrifugation for 60 minutes at 3500 X g followed by extraction and gas-chromatography as a rapid, valid way to measure the P/S ratio.

Arachidonic acid is considered to be one of the precursors in prostaglandin synthesis. For this reason, arachidonic acid was measured in a series of amniotic fluid. Samples in order to rest the hypothesis that the beginning of uterine activity is accompanied by a rise of its concentration. In fact, it could be shown that in amniotic fluid from patients in labor arachidonic acid levels are much higher than in amniotic fluid from patients without uterine activity.

Assessment of foetal lung maturity by gas chromatographic analysis of the fatty acids in the amniotic fluid. Statistical reliability of the technique. Gas-chromatographic analysis of the fatty acids (Palmitis acid/Steric acid ratio: P/S ratio) was carried out in 432 samples of amniotic fluid obtained between the 28th and 42th weeks of gestational age. The present results from a series of normal (257) and various pathological (175) cases support the conclusions of other investigations that an amniotic fluid P/S ratio equal to or greater than 5 is a reliable indicator of attained fetal lung maturity. When correlated with gestational age the P/S ratios show regression lines that define the range of lung maturity in normal pregnancies between 32 and 33 weeks and in pathological cases around and over 36 weeks. Statistical studies stress that centrifugation in standard sample conditions before its gas chromatographic analysis is an essential step in order to avoid the serious consequences of an erroneous prediction. Finally Lecithin/Sphingomyelin (L/S) and P/S ratios were assessed in the same 100 samples of amniotic fluid: statistical analysis shows a very good correlation between the two methods and their reliability in the prediction of fetal lung maturity.

Gas-chromatographic analysis of the fatty acids (P/S ratio) in 212 samples of amniotic fluid, 35 samples of vernix caseosa and 35 samples of the pellets obtained after centrifugation of the amniotic fluid were carried out to evaluate the effects of contaminants that might be present in amniotic fluid on the P/S ratio. The P/S ratio is used as an index of the degree of maturity of the fetal or neonatal lungs. Analysis of variance applied to the means of the P/S values for each of above materials showed them to be significantly different and attests to the importance of centrifugation for obtaining valid results. We propose a standard procedure of centrifugation for 60 minutes at 3500 X g followed by extraction and gas-chromatography as a rapid, valid way to measure the P/S ratio.