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Biomedical subjects

E Falleti

Publications and source records attributed to E Falleti.

At least 19 recordsLinked to original sources
PubMed2001

Serum iron indices as a measure of iron deposits in chronic hepatitis C.

Serum iron indices are believed to be elevated in patients with hepatitis C virus (HCV) infection in connection to the presence of hepatic inflammation, though this hypothesis has never been formally tested. We studied 69 consecutive, unselected anti HCV antibody positive patients, aged 14 to 70 years. Iron, transferrin saturation and ferritin were measured in fasting serum samples. Histologically detectable iron (HDI) as well as histologic grading and staging were estimated semiquantitatively in liver biopsy samples. The median values for serum iron, transferrin saturation and serum ferritin were 24 micromol/l (range, 8-61), 29 percent (range, 6-77) and 170 microg/l (range, 1-954), respectively. At univariate analysis, all three serum iron indices were positively correlated with grading and staging scores, as well as with HDI in the liver; only serum iron was positively correlated with transaminases. At multivariate analysis, independent associations were found between serum iron and the grading score; ferritin and sinusoidal and portal HDI; transferrin saturation and total hepatic HDI. In conclusion, in hepatitis C, serum iron reflects the degree of current hepatic inflammation and necrosis, whereas the extent of progressive deposition of iron in sites of fibrosis is best reflected by serum ferritin. Transferrin saturation is the best predictor of the status of hepatic iron deposits.

Adolescent↗
PubMed2000

Endotoxin priming and liver damage by experimental duodenal obstruction in the rat.

To verify whether endotoxin (LPS) might act as a priming cofactor of liver injury caused by obstructing the duodenum, four groups of male Wistar rats were studied. The first two groups comprised rats in which a closed duodenal loop (CDL) was created: CDL, n = 6 and CDL + LPS, n = 7; the next two groups comprised sham-operated animals: Sham n = 6 and Sham + LPS, n = 6. LPS, 400 microg/kg bodyweight, was administered i.p. to the rats belonging to groups CDL + LPS and Sham + LPS, 24 h before laparotomy. Twenty-four hours after laparotomy the animals were killed. Damage to bile ducts, extent and grading of coagulative and lytic spotty necrosis in liver tissue were evaluated morphologically. Coagulative necrosis was severe in four of seven rats of the group CDL + LPS, mild in six of six rats of group CDL, and absent in four of six and five of six rats of groups Sham and Sham + LPS (chi2 32.8, P = 0.0001). The animals of group CDL + LPS had more frequently diffuse lytic spotty necrosis than the animals in the three other groups (chi2 9.57 P<0.01). The results of our study indicate that, in rodents subjected to a closed duodenal loop, priming with LPS exacerbates liver injury due to cholate stasis.

Alanine Transaminase↗
PubMed1999

Effect of eating on plasma radical-trapping antioxidant activity (TRAP) in patients with cirrhosis.

OBJECTIVES: To ascertain the effects of eating on plasma antioxidant capacity in patients with liver disease. DESIGN AND METHODS: Eighteen cirrhotic patients were compared to 18 age and sex-matched controls. TRAP was measured by a fluorometric assay after a 12 h fast, and 60, 120, and 180 min after the study participants had taken a drink formula food. RESULTS: In the fasting state, TRAP was higher in patients with alcoholic cirrhosis (847+/-39 micromol/L, mean +/- SEM) in comparison to patients with viral cirrhosis (653+/-41) and to controls (758+/-26) (p<0.005). In cirrhotic patients, TRAP did not change in the post-absorptive state. In controls, TRAP decreased progressively, to a value of 719+/-21 (p<0.02), and the AUC of the delta-values of TRAP and of plasma insulin showed an inverse correlation (r = -0.52, p<0.05). CONCLUSIONS: In normal subjects, but not in cirrhotics, TRAP decreases in the post-absorptive state, probably in relationship with the activation of metabolic pathways.

Antioxidants↗
PubMed1999

IgM antibody response to the hepatitis C virus core protein in intravenous drug users.

To verify whether a solid-phase enzyme immunoassay for serum IgM antibodies to the hepatitis C virus (HCV) core protein (IgM anti-HCVcore) might be proposed as a surrogate test for serum HCV RNA, we studied 86 anti-HCV antibody-positive intravenous drug users. Serum HCV RNA was demonstrated by RT-PCR with primers derived from the 5' non-coding and the core region. IgM anti-HCVcore antibodies were found in 62/86 (72%) subjects; circulating HCV RNA was detected by the 5' noncoding assay in 53/86 samples (62%) and by the core region assay in 35/86 samples (41%). IgM anti-HCVcore reactivity was associated with core HCV RNA seropositivity (p < 0.05) but not with 5' noncoding HCV RNA seropositivity (p = NS). Patients infected by HCV type 1a were more-often positive for IgM anti-HCVcore (p < 0.05) and for core HCV RNA (p = 0.005) than patients infected by other HCV genotypes. IgM anti-HCVcore reactivity was significantly more common in subjects positive for core HCV RNA (p < 0.005) and in subjects aged > 30 years (p < 0.05). In conclusion, the IgM anti-HCVcore assay frequently tests positive in intravenous drug users, particularly when infected by HCV 1a, but is not a surrogate of testing for serum HCV RNA.

Adult↗
PubMed1999

Kinetics of serum soluble tumour necrosis factor receptor (TNF-R) type-I and type-II after a single interferon-alpha (IFN-alpha) injection in chronic hepatitis C.

Circulating soluble TNF receptors, which act as TNF inhibitors, increase following the administration of IFN-alpha. Whether this is due to a direct IFN action or to indirect mechanisms involving the release of other cytokines is unclear. The kinetics of serum IFN, TNF, IL-6, IL-10, soluble TNF receptor type-I (sTNF-RI) and sTNF-RII were evaluated by enzyme immunoassays in 11 patients with chronic hepatitis C, following the first dose of recombinant human IFN-alpha2b (3 MU given subcutaneously). sTNF-RI concentrations paralleled IFN concentrations, rising from a mean +/- s.e.m. value of 3.5 +/- 0.3 ng/ml at baseline to a peak value of 5.5 +/- 0.5 ng/ml after 9 h, followed by a return to 4.1 +/- 0.4 ng/ml after 24 h (P = 0.0001). sTNF-RII concentrations, which were 7.6 +/- 0.5 ng/ml at baseline, fell initially to 6.9 +/- 0.5 ng/ml, to reach a peak at 24 h of 9.0 +/- 0.7 ng/ml (P < 0.0001). In contrast, the concentrations of TNF, IL-6 and IL-10 fluctuated with no significant changes at any time point. The area under the curve (AUC) of incremental IFN values had a strong positive correlation with the AUC of incremental sTNF-RI values (r = 0.75, P < 0.01). In patients with hepatitis C, IFN concentrations reached after a single dose of IFN were paralleled by correlationally increased concentrations of sTNF-RI, which are a much better marker of administered IFN than sTNF-RII, IL-6 or IL-10.

Adult↗
PubMed1999

The influence of furosemide on free water clearance.

BACKGROUND: Laboratory measurements of osmolality and electrolyte concentrations are useful as a source of clinical and pathophysiologic information on kidney function. We obtained different conditions of baseline diuresis in 54 rats, which were then treated with furosemide 10 mg/kg. From measurements of plasma (P) and urine (U) osmolality and Na, we calculated the free water clearance (CH2O) and the contributions of Na+ and non-Na(+)-solutes to its changes during diuretic administration. RESULTS: The results show that furosemide abolishes both urine diluting and concentrating ability, by reducing the contribution of non-Na(+)-solutes to Uosm and the formation of CH2O, while the contribution of Na+ to Posm remains unchanged. During furosemide the urines approach isosmoticity irrespective of the baseline Uosm with an asymptomatic function similar to that imposed by osmotic diuresis. It is suggested that the overflow to the concentrating sites of the nephron overwhelms their normal transport capacity independently of their baseline water permeability. The disruption of the transepithelial osmotic gradient caused by the drug impairs the transepithelial osmotic flow, leading to the excretion of isosmotic urines. CONCLUSIONS: The effect of non-Na(+)-solutes in the laboratory measurement of urine constituents can be reduced to that of plasma determination by diluting the urines according to empiric formulas derived from the present data.

Animals↗
PubMed1998

Increased serum lipoprotein(a) levels in patients with early renal failure.

BACKGROUND: Elevated serum lipoprotein(a) levels have been found in patients with end-stage renal disease and in patients undergoing dialysis, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. It is not known whether lipoprotein(a) levels are elevated in the early phases of renal disease. OBJECTIVE: To evaluate levels of lipoprotein(a) and other lipids and the prevalence of atherosclerotic disease in patients with early renal failure. DESIGN: Cross-sectional study. SETTING: Hypertension clinic of a university medical center. PATIENTS: 257 patients with normal renal function and 160 patients with early impairment of renal function (creatinine clearance, 30 to 89 mL/min per 1.73 m2 of body surface area). MEASUREMENTS: Renal function was assessed by 24-hour creatinine clearance, proteinuria, and microalbuminuria. Cardiovascular disease status was also assessed. Serum lipoprotein(a), lipids, apolipoproteins, and apolipoprotein(a) isoforms were measured. RESULTS: Age, blood pressure, and serum lipoprotein(a) levels were greater in patients with early renal failure than in those with normal renal function and were independently associated with the presence of decreased creatinine clearance. Serum lipoprotein(a) and creatinine clearance were inversely correlated. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was greater in patients with early renal failure than in those with normal renal function. The frequency distribution of apolipoprotein(a) isoforms was similar in patients with normal and those with impaired renal function. CONCLUSIONS: Serum lipoprotein(a) levels are elevated in patients with early impairment of renal function and are associated with greater prevalence of cardiovascular disease. An inverse correlation between serum lipoprotein(a) level and creatinine clearance and a frequency distribution of apolipoprotein(a) isoforms similar to that of normal patients point to decreased renal catabolism as a probable mechanism of lipoprotein(a) elevation in patients with early renal failure.

Adult↗
PubMed1998

Factors associated with serum HCV RNA positivity in anti-HCV antibody positive intravenous drug users.

Serum hepatitis C virus (HCV) RNA, HCV genotypes and liver function tests were evaluated in a series of 189 unselected, consecutive anti-HCV positive intravenous drug users (IVDUs). Serum HCV RNA was detected in 106/189 patients. Abnormal liver function tests were associated with alcohol abuse, but not with the presence of serum HCV RNA. Among 109 patients retested after a mean follow-up of 21 months, 41 were intermittently serum HCV RNA positive. Patients persistently negative had more commonly a past history of acute hepatitis. A history of prostitution and/or a pattern of abuse involving >30 injections per week were related to infection by genotype 3a. In conclusion, serum HCV RNA is either transiently or persistently detectable in most anti-HCV positive IVDUs, but bears no association with abnormal liver biochemistry. Infection by HCV-3a is more common in IVDUs with more deviant life styles. In those cases where serum HCV RNA is found repeatedly negative, HCV infection may have been cleared, possibly through an episode of acute hepatitis.

Adult↗
PubMed1998

Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress.

ICAM-1 is one of the most important intercellular adhesion molecules involved in atherogenesis. Previous studies reported increased circulating ICAM-1 plasma levels in NIDDM patients with or without vascular complications. It has been suggested that an acute increase of plasma glucose may produce an oxidative stress in man, and in vitro studies have demonstrated that high glucose and free radicals induce cellular expression of ICAM-1. In this study, three different experiments were performed in nine NIDDM patients and in seven matched healthy controls: oral glucose tolerance test, antioxidant glutathione i.v. administration for two h, oral glucose tolerance test plus glutathione i.v. administration. Blood samples were drawn at -15 min and every 30 min from 0 to 180 min. During the oral glucose tolerance test, circulating ICAM-1 plasma levels significantly increased in both diabetic and normal subjects. Glutathione administration during the oral glucose tolerance test abolished this phenomenon. Glutathione administered alone significantly decreased circulating ICAM-1 plasma levels in diabetic patients, while no effect was observed in the normal subjects. These data suggest that hyperglycemia may induce an increase of circulating ICAM-1 plasma levels through an oxidative stress, and that the antioxidant glutathione counterbalances this effect. These data support the hypothesis of a causal relationship linking hyperglycemia, oxidative stress and atherogenesis in diabetes mellitus.

Aged↗
PubMed1998

Relationship among hepatic inflammatory changes, circulating levels of cytokines, and response to IFN-alpha in chronic hepatitis C.

To investigate the relationship among circulating cytokines, inflammation in the liver, and kind of response to interferon-alpha (IFN-alpha) in hepatitis C, we studied 63 consecutive patients (38 male, 25 female), treated with IFN for up to 1 year. Serum tumor necrosis factor-alpha (TNF-alpha) was measured at baseline and after 3 months of treatment. Transient (TR) or sustained response (SR) was observed in 29 and 16 patients, respectively. Baseline levels of TNF < or = 22 ng/L were observed in 69% of patients with SR, 55% of patients with TR, and 22% of nonresponders (p < 0.01). There was a significant correlation between baseline TNF levels and histologic grading score of hepatitis (p < 0.01). After 3 months of treatment, TNF levels >22 ng/L were observed in 63% of patients with SR, 69% of patients with TR, and 83% of nonresponders (p NS). Independent of the treatment outcome, TNF levels were lower at baseline and increased significantly with treatment in patients with lower histologic grading (p < 0.005). In conclusion, in patients with chronic hepatitis C, circulating TNF levels correlate with the degree of inflammation in the liver. Response to IFN is accompanied by an inflammatory response involving the release of TNF.

Adult↗
PubMed1998

Circulating levels of interleukin 10 and other cytokines in rheumatoid arthritis treated with cyclosporin A or combination therapy.

OBJECTIVE: To assess longitudinally over a 12 month period circulating serum levels of interleukin 10 (IL-10) and cytokines IL-3, IL-4, IL-6, and IL-12 in a cohort of patients with early onset rheumatoid arthritis (RA) treated with either cyclosporin A (CyA) or with combination therapy of CyA plus hydroxychloroquine as disease modifying antirheumatic drugs. METHODS: We studied 8 patients receiving CyA and 12 patients receiving CyA plus hydroxychloroquine. IL-3, IL-4, IL-6, IL-10, and IL-12 were determined by ELISA at entry, after 2 weeks, after one month, after 6 months, and after 12 months. Rheumatoid factor levels and the possible appearance of monoclonal gammopathies over time were studied by immunofixation and immunoblotting techniques. RESULTS: The pooled data show that at entry only the median baseline levels of IL-10 (3.9 vs 1.6 pg/ml; p < 0.01) and IL-6 (16.9 vs 1.4 pg/ml, p < 0.001) were higher in patients than in controls. IL-4 was not detectable. Some patients at entry (those with the longest disease duration) had detectable levels of IL-3. Only levels of IL-10 decreased significantly between entry and final values, in monotherapy and combination therapy as well. A single transient monoclonal band was observed after 6 months of treatment, which disappeared afterwards. No difference was seen in any of the cytokines between the CyA and the CyA plus hydroxychloroquine treated patients. CONCLUSION: During treatment with either CyA or CyA plus hydroxychloroquine, IL-10 levels decreased significantly. No additive effect of the 2 drugs was detected.

Adolescent↗
PubMed1997

Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension.

OBJECTIVE: To investigate the association between lipoprotein(a) [Lp(a)] and other plasma lipids and apolipoproteins and target-organ damage (TOD) in patients with arterial hypertension. DESIGN: Cross-sectional study of a case series. SETTING: University medical center. PARTICIPANTS: Lipoprotein(a) and apolipoproteins were analyzed in 277 untreated patients with mild to moderate essential hypertension and in 102 healthy controls. Apolipoprotein(a) [apo(a)] phenotypes were additionally analyzed in an independent sample set of 106 hypertensive and 105 control subjects. MAIN OUTCOME MEASURES: Staging of TOD obtained according to World Health Organization guidelines by clinical evaluation, and laboratory tests including measurments of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries; levels of lipids, apolipoproteins, Lp(a), fibrinogen, and apo(a) phenotypes. RESULTS: Blood pressure, duration of hypertension, and levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, Lp(a), and fibrinogen were significantly related to the presence and severity of TOD in univariate analysis. Stepwise multivariate analysis showed Lp(a) levels (P<.001) to be the best discriminator of the presence of TOD, followed by systolic blood pressure (P<.001), duration of hypertension (P=.01), and low-density lipoprotein cholesterol (P=.04). The Lp(a) levels were related to TOD independent of the level of blood pressure. We confirmed this association between Lp(a) concentrations and severity of TOD in a second independent sample set and observed a significantly higher frequency of low-molecular-weight apo(a) isoforms with increasing severity of TOD (P=.02). CONCLUSIONS: Lipoprotein(a) and apo(a) phenotype are sensitive indicators of the severity of TOD in patients with essential hypertension, and their evaluation might permit identification of hypertensive subjects liable to the development of organ damage. The higher frequency of low-molecular-weight apo(a) isoforms in patients with TOD demonstrates a genetically determined risk for the development of TOD in hypertensive patients.

Adult↗
PubMed1997

Blood lipids of patients with chronic hepatitis: differences related to viral etiology.

In order to investigate whether a difference might exist in blood cholesterol and its subtractions between patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, serum cholesterol, HDL-cholesterol, triglycerides and common liver function tests were measured in 138 patients (92 male, 46 female) with biopsy-proven chronic viral hepatitis without cirrhosis. Twenty-four had hepatitis B and 114 hepatitis C. Mean serum cholesterol was lower in HCV-infected in comparison to HBV-infected patients (175 +/- 36 mg/dl vs. 189 +/- 28 mg/dl, p < 0.05). On multivariate analysis, etiology of hepatitis appeared to be associated with the value of serum cholesterol, independently of age, sex and liver synthetic function (improvement of chi-square 4.40, p < 0.05). In patients with HBV infection, circulating tumor necrosis factor-alpha demonstrated a correlation with serum triglycerides (p = 0.618) and an inverse correlation with serum HDL-cholesterol (p = -0.456); in the group of patients with HCV infection, interleukin-6 correlated with triglycerides (p = 0.370) and HDL-cholesterol (p = -0.355). Thus, differences in the mechanisms of liver damage and of viral clearance in hepatitis C in comparison to hepatitis B, reflected in these patients by the levels of circulating cytokines, may be mirrored by differences in their blood lipid composition.

Adult↗
PubMed1997

Circulating standard CD44 isoform in patients with liver disease: relationship with other soluble adhesion molecules and evaluation of diagnostic usefulness.

OBJECTIVES: To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. METHODS: We studied 142 subjects (90 male, 52 female): 14 had acute hepatitis (AH); 45, noncirrhotic chronic liver disease (CLD); 34, cirrhosis; 35 had extrahepatic diseases (EHD); and 14 were healthy controls. sCD44, soluble intercellular adhesion molecule-1 (slCAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured immunoenzymatically. RESULTS: Patients with AH or cirrhosis had higher sCD44 in comparison to CLD, EHD, and controls (p < 0.01). On univariate analysis, sCD44 was associated with sVCAM-1, sICAM-1, bilirubin, cholinesterase, aspartate aminotransferase, and alkaline phosphatase (p < 0.001). By stepwise discriminant analysis, a set of variables, including sCD44 and sVCAM-1, were entered into a model that allocated correctly 79% of observations (p < 0.0001). However, when adhesion molecules were excluded, the model could still allocate correctly 72% of observations. CONCLUSION: Although sCD44 concentration increases during severe acute or chronic liver disease, its measurement adds little to the clinical information provided by traditional liver biochemistry.

Acute Disease↗
PubMed1997

Endogenous interferon-alpha concentration and outcome of interferon treatment in patients with chronic hepatitis C.

To verify its value with regard to the outcome of therapy in chronic hepatitis C, serum interferon-alpha (IFN) was measured by ELISA in 70 patients (43 male, 27 female) with chronic hepatitis C, treated with IFN 9 MU/week subcutaneously for up to one year. Serum IFN was detectable in 49/70 patients, 16 of whom had IFN values >125 pg/ml. Only 1/22 patients who maintained a sustained response six months after the end of treatment had pretreatment serum IFN > 125 pg/ml, in comparison to 15/48 patients who did not respond or who relapsed (chi2 6.1, P < 0.02). At multivariate analysis the predictive value of serum IFN was independent of age, sex, presence of cirrhosis, infection by genotype 1b (improvement chi2 7.1, P < 0.01). In patients with chronic hepatitis C, measurement of serum IFN at baseline might be useful for the selection of patients with higher probability of long-term response.

Adolescent↗
PubMed1997

Increased soluble ICAM-1 concentration and impaired delayed-type hypersensitivity skin tests in patients with chronic liver disease.

AIMS/BACKGROUND: Soluble ICAM-1 may act as an antagonist of the membrane bound form, which is essential for the adhesion of leucocytes to endothelial cells. The aim of this study was to investigate whether the presence of high concentrations of soluble ICAM-1 are related to the impairment of delayed-type hypersensitivity reactions. METHODS: The study population comprised 73 patients (53 men and 20 women) with chronic liver disease (19 with chronic hepatitis, 36 with cirrhosis and 18 with hepatocellular carcinoma), and 21 age-matched controls (11 men and 10 women). Serum soluble ICAM-1 was measured using an enzyme immunoassay. Skin tests for seven different antigens (tetanus, diphtheria, streptococcus group C, tuberculin, Candida, tricophyton, and proteus) were considered positive when diameters > or = 2 mm were recorded; the diameters of positive tests were added to calculate a cumulative score. RESULTS: Patients with chronic liver disease had fewer positive skin tests (median 2) and a lower cumulative score (median 7) than controls (median 3 and 12, respectively). Multivariate analysis suggested the existence of an independent association between alkaline phosphatase and anergy to skin tests and between soluble ICAM-1 concentrations and the cumulative score. CONCLUSIONS: The strong association observed between increased soluble ICAM-1 concentrations and impairment of delayed-type hypersensitivity skin tests suggests that soluble ICAM-1 may be implicated in the immune depression seen in patients with chronic liver disease.

Adult↗
PubMed1997

A comparison of four serum markers of fibrosis in the diagnosis of cirrhosis.

C-terminal peptide of procollagen I, N-terminal peptide of procollagen III, collagen IV and serum prolyl hydroxylase were measured in 100 patients with cirrhosis and 71 patients with noncirrhotic chronic liver disease. Patients with cirrhosis had significantly higher mean values of prolyl hydroxylase, collagen IV, N-terminal peptide of procollagen III and C-terminal peptide of procollagen I as compared to noncirrhotic patients. This difference was maintained for collagen products even after stratification for alcohol intake, although all markers of fibrosis were higher in alcoholics. Stepwise logistic regression analysis showed that collagen IV, and N-terminal peptide of procollagen III were independently associated with cirrhosis. Receiver-operating characteristic (ROC) curves showed that collagen IV and N-terminal peptide of procollagen III perform more efficiently than C-terminal peptide of procollagen I and prolyl hydroxylase in identifying cirrhosis.

Adult↗