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Biomedical subjects

M Pirisi

Publications and source records attributed to M Pirisi.

At least 37 records · Page 2Linked to original sources
PubMed1998

High prevalence of infection with hepatitis G virus in patients with hepatic and extrahepatic malignancies.

BACKGROUND/AIMS: The pathogenic role of hepatitis G virus, the recently discovered blood-borne agent, is controversial. Our aim was to ascertain the prevalence of hepatitis G virus infection in hepatic and in extrahepatic malignancies. METHODS: We studied 166 Italian patients (112 male, 54 female, mean age 61.8+/-9.3, mean+/-SD, range 34-85). One hundred and eighteen had cirrhosis, which was complicated by hepatocellular carcinoma in 66 cases. Forty-eight patients had extra-hepatic malignancies. Circulating HGV RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) of both the nonstructural-3 and 5'noncoding regions of the hepatitis G virus genome. Antibodies to the E2 protein of hepatitis G virus were detected by means of an enzyme-linked immunosorbent assay. RESULTS: Ongoing HGV infection was detected in 30/66 (46%) patients with hepatocellular carcinoma, 12/52 (23%) patients with cirrhosis, and 14/48 (29%) patients with extrahepatic malignancies (p<0.05). Evidence of exposure to hepatitis G virus (detection of either HGV RNA or anti-E2 antibodies) was found in 46% of patients with cirrhosis, 66% of patients with hepatocellular carcinoma, and 39% of patients with extrahepatic malignancies. Serum HGV RNA positivity was associated with a hematocrit value < or = 0.35 and with history of exposure to blood products (p<0.005). CONCLUSIONS: Ongoing hepatitis G virus infection is detected at a very high rate in patients with hepatocellular carcinoma, but is also fairly common in extrahepatic malignancies. Hepatitis G virus infection in these patients is likely to originate from exposure to blood products, and to persist because of deficient immune surveillance.

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

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↗
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

Chronic lymphocytic sialoadenitis in HCV-related chronic liver disease: comparison of Sjögren's syndrome.

With the aim of morphologically characterizing chronic sialoadenitis in patients with hepatitis C virus (HCV) chronic liver disease, labial salivary gland biopsies from 22 chronic HCV liver disease and from 10 primary Sjögren's syndrome patients were compared. Only focus score (number of aggregates with more than 50 lymphocytes per 4 mm2 of glandular tissue) and grading of inflammation were able to discriminate significantly between the two patient groups. Duct ectasia, acinar depletion, presence of lymphoid aggregates with less than 50 lymphocytes and of lymphoid infiltration within intralobular salivary duct epithelium were evident in both disease groups and appeared to be non-specific, mostly age-related changes. In both patient groups plasma cell and lymphocyte typing showed similar features: T-lymphocytes represented most of the lymphoid population, B lymphocytes were few unless follicles were present. Higher focus score values were associated with a plasma cell switch from an IgA to an IgM and/or IgG predominance. A greater morphological similarity was seen between biopsies of the primary Sjögren's syndrome group and those of female rather than male chronic HCV liver disease patients. Salivary gland tissue in HCV patients responds to damage in a fashion similar to primary Sjögren's syndrome, the only difference being a lesser degree of inflammation.

Adult↗
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↗
PubMed1997

Total plasma antioxidant capacity predicts thrombosis-prone status in NIDDM patients.

OBJECTIVE: To explore the hypothesis that a relationship exists between free radical activity and abnormalities in hemostasis in NIDDM. RESEARCH DESIGN AND METHODS: The use of the total radical-trapping antioxidant parameter (TRAP) has very recently been proposed to explore the antioxidant property of a plasma and their mutual cooperation. In the present study, TRAP, vitamin E, vitamin C, vitamin A, uric acid, protein-bound SH (thiol) groups, fibrinogen, prothrombin fragments F1 + 2, and D-dimer have been evaluated in 46 NIDDM patients and 47 healthy matched control subjects. RESULTS: In NIDDM patients, TRAP, vitamin A, SH groups, and uric acid were significantly reduced, whereas the level of vitamin E was significantly increased. Vitamin C was similar in the two groups. Fibrinogen, prothrombin fragment 1 + 2, and D-dimer were increased in diabetic patients. TRAP, but no single other antioxidant, had a strong inverse association with fibrinogen, prothrombin fragment 1 + 2, and D-dimer. CONCLUSIONS: These findings are consistent with the hypothesis that oxidative stress may condition coagulation activation in diabetics. However, the data suggest that it is the total antioxidant capacity rather than any single plasma antioxidant that is the most relevant parameter.

Antioxidants↗
PubMed1996

Post-meal coagulation activation in diabetes mellitus: the effect of acarbose.

It has been previously demonstrated that hyperglycaemia activates haemostasis; diabetes mellitus is considered a thrombosis-prone state. Acarbose, by inhibiting dietary carbohydrate absorption, reduces post-meal hyperglycaemia. In this study we evaluated the effect of post-meal hyperglycaemia on two markers of coagulation activation: prothrombin fragments 1 + 2 and D-dimer. Seventeen non-insulin-dependent diabetic patients maintained on diet therapy alone were randomly assigned to receive- with a cross-over study design-acarbose (100 mg orally) or placebo before a standard meal. Blood samples for measurement of plasma glucose, insulin, prothrombin fragments 1 + 2 and D-dimer were drawn at 0, 60, 120 and 240 min. After both placebo and acarbose, hyperglycaemia and hyperinsulinaemia which followed a standard meal were accompanied by a significant increase of plasma concentration of prothrombin fragments 1 + 2 and D-dimer in comparison to their baseline values. Acarbose administration significantly reduced the rise of glucose, insulin, prothrombin fragments 1 + 2 and D-dimer from 0 to 240 min in comparison to placebo. We conclude that post-meal hyperglycaemia, at the level reached by many diabetic patients on diet therapy alone, induces a coagulation activation. Acarbose, by decreasing post-meal hyperglycaemia, may be useful in reducing meal-induced activation of haemostasis in diabetic patients.

Acarbose↗
PubMed1996

Circulating intercellular adhesion molecule 1 predicts non-specific elevation of alpha 1-fetoprotein.

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of alpha 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R = -0.397, P < 0.001), aspartate aminotransferase (R = 0.421, P < 0.001), bilirubin (R = 0.231, P < 0.05) and cICAM-1 (R = 0.430, P < 0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.

Adult↗
PubMed1996

Endotoxin priming exacerbates acute reflux pancreatitis in the rat.

Recently, endotoxaemia has been reported as a prognostic marker in acute pancreatitis. However, the role of endotoxin in inducing or aggravating acute pancreatitis is not fully understood. We administered endotoxin 400 micrograms/kg i.p. to rats 24 h before performing either a closed duodenal loop (group B) or a sham operation (group D). Pancreatic damage and overall survival were compared with the results obtained in rats not exposed to endotoxin undergoing either closed duodenal loop (group A) or sham treatment (group C). In a first set of experiments, 24 h after laparotomy blood samples were collected and the animals were sacrificed; survival up to 8 days was estimated in a second set of experiments. Group B had higher lipase concentrations and more severe tissue damage than group C (P < 0.05). A larger number of abscesses was observed in both group B and group D as compared to group C (P < 0.05). Survival was significantly shorter in group B (P < 0.0001). We conclude that priming with endotoxin worsens the extent of pancreatic damage induced by the closed duodenal loop procedure in the rat, possibly favouring selective homing of neutrophils to the site of inflammation, in similarity to what happens in the Shwartzman phenomenon.

Animals↗
PubMed1996

Prognostic value of serum alpha-1-antitrypsin in hepatocellular carcinoma.

To evaluate serum alpha-1-antitrypsin (A1AT) as a prognostic factor in hepatocellular carcinoma, we studied 75 consecutive patients (60 male, 15 female, mean age +/- SD 63.0 +/- 9.3 years) in whom hepatocellular carcinoma developed with pre-existing cirrhosis. Median survival time was 245 days (range 4-1568+). 30 patients had serum A1AT concentration of < or = 2.20 g/l (Group A) while 45 (Group B) had alpha-1-antitrypsin > 2.20 g/l. Median survival was 518 days in Group A and 81 days in Group B (Mantel-Cox 20.95, P < 0.0001; hazard ratio 0.26, 95% confidence limits 0.15-0.46). By stepwise survival analysis, alpha-1-antitrypsin together with bilirubin, tumour size and blood urea nitrogen were chosen among 17 variables as the only independent predictors of survival. We conclude that measurement of serum A1AT concentration might be useful as an inexpensive, widely available prognostic marker of hepatocellular carcinoma.

Adult↗
PubMed1996

Immunosuppressive treatment of Berger's disease.

BACKGROUND: The aim of our study was to determine whether immunosuppressive treatment is effective in preventing and reversing the evolution of Berger's disease toward chronic renal failure. METHODS: We studied 20 unselected, consecutive patients with biopsy-proven Berger's disease who met the criteria for disease progression. They had proteinuria, significant histologic changes, persistent hematuria, and red cell casts. The treatment consisted of prednisone in an alternate-day regimen and cyclophosphamide, either in a daily oral administration or in a monthly intravenous pulse injection, both given for a 6-month cycle. Five patients had chronic renal failure (as disclosed by plasma creatinine of 230 +/- 71 mumol/L), hypertension, and proteinuria (2.7 +/- 0.8 gm/day), whereas the remaining 15 patients had normal renal function (plasma creatinine, 97 +/- 18 mumol/L) and less severe proteinuria (1.9 +/- 1.1 gm/day). However, even these 15 patients had a significant number of risk factors heralding progression to chronic renal failure. RESULTS: Over an average follow-up of 8.7 +/- 3.7 years (range, 5 to 15 years), all patients but one had complete disease remission, including five patients with incipient chronic renal failure. Relapse occurred in two patients who were healed after a repeat treatment cycle. Over the entire follow-up period, no patient progressed to chronic renal failure and plasma creatinine concentration remained stable, even in subjects in whom it was high before treatment (257 +/- 79 versus 230 +/- 71 mumol/L; p > 0.05). CONCLUSION: The immunosuppressive treatment of patients with Berger's disease with high probability of progression appears to be effective in the prevention of end-stage renal disease.

Adolescent↗
PubMed1996

Regression of Henoch-Schönlein disease with intensive immunosuppressive treatment.

OBJECTIVE: To assess the results of a new immunosuppressive cycle, which had given favorable results in other immune-mediated glomerulonephritides, in the treatment of Henoch-Schönlein disease. METHODS: Eight patients (seven male and one female; age range, 13 to 61 years) with biopsy-proved Henoch-Schönlein were treated with the following protocol: (1) induction with 250 to 750 mg intravenous methylprednisolone every day for 3 to 7 days plus 100 to 200 mg oral cyclophosphamide every day, (2) maintenance with 100 to 200 mg oral prednisone on alternate days plus cyclophosphamide, as before, for 30 to 75 days; (3) tapering, with prednisone reduced on average by 25 mg every month while the cyclophosphamide dose remained the same, and (4) discontinuation, after at least 6 months, with abrupt interruption of cyclophosphamide and slow tapering of prednisone. The results were assessed in terms of remission, improvement, progression of disease, kidney failure, and death, unambiguously defined. The follow-up extended up to 12 years. RESULTS: Seven of eight patients had a complete remission that was maintained indefinitely thereafter. Plasma creatinine levels decreased on average from 211 +/- 81 to 92 +/- 27 mumol/L (p < 0.01) and urine protein excretion decreased from 1.9 +/- 0.8 to 0.3 +/- 0.1 gm/day (p < 0.01). One patient died of intestinal infarction caused by atherosclerotic mesenteric artery thrombosis. CONCLUSIONS: Our data suggest that an intensive immunosuppressive regimen that combines prednisone and cyclophosphamide at high doses can be effective in healing Henoch-Schönlein disease.

Administration, Oral↗
PubMed1996

Discordant results from hepatitis C virus genotyping by procedures based on amplification of different genomic regions.

We compared the results of genotyping hepatitis C virus (HCV) either by PCR amplification of the core region or by hybridization of PCR-amplified products of the 5' untranslated region (5'UTR assay). Serum samples from 144 Italian anti-HCV-positive patients (106 drug abusers and 38 patients with chronic viral liver disease but no history of drug abuse) were studied. The original core region assay described by Okamoto et al. (H. Y. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyakawa, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) allowed genotyping of 75 of 144 samples. A modified version of Widell et al. (A. Widell, S. Shev, S. Månsson, Y.-Y. Zhang, U. Foberg, G. Norkrans, A. Frydén, O. Weiland, J. Kurkus, and E. Nordenfelt, J. Med. Virol. 44:272-279, 1994) allowed genotyping of 11 of 79 samples (50 of 79 samples remained unclassified by the method of Okamoto et al. In contrast, all 144 samples were genotyped by the 5'UTR assay. Forty-six of 75 (61 percent) of the samples genotyped by the method of Okamoto et al. and 10 of 11 (91 percent) of the samples genotyped by the method of Widell et al. had results consistent with those obtained by the 5'UTR assay. According to the results of direct sequencing, the method of Okamoto et al. erroneously classified seven samples as having mixed infections. In conclusion, HCV genotyping seems more reliable when it is performed by the 5'UTR assay than by either of two core region assays. The major advantage provided by the 5'UTR assay is a much lower proportion of negative or indeterminate results in younger patients with histories of drug abuse or infection by genotypes other than HCV type 1.

Adolescent↗