R. Corrocher - Academia.edu (original) (raw)

Papers by R. Corrocher

Research paper thumbnail of Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn’s disease

Journal of Internal Medicine, 2009

Lunardi C, Bason C, Dolcino M, Navone R, ). Antiflagellin antibodies recognize the autoantigens T... more Lunardi C, Bason C, Dolcino M, Navone R, ). Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn's disease. J Intern Med 2009; 265: 250-265.

Research paper thumbnail of STIMA DELLA PREVALENZA DELL'IPERTENSIONE ARTERIOSA E DI ALTRI FATTORI DI RISCHIO CARDIOVASCOLARE NELLA POPOLAZIONE GENERALE RESIDENTE NELL'ASL 22 DELLA REGIONE VENETO

Finanziamenti: lavori eseguiti per conto della Regione Veneto, Giunta regionale -Ricerca Sanitaria

Research paper thumbnail of Ischemic Colitis Sustained by Sickle Cell Trait in Young Adult Patient

The American Journal of Gastroenterology, 2005

TO THE EDITOR: A 44-yr-old Brazilian woman was admitted to our Unit on October 2002 for abdominal... more TO THE EDITOR: A 44-yr-old Brazilian woman was admitted to our Unit on October 2002 for abdominal pain. Abdominal examination revealed decreased bowel sounds without guarding or rigidity. ... To read this article in full you may need to log in, make a payment or gain ...

Research paper thumbnail of Changes of fatty acid composition and oxidative metabolism of human neutrophils migrating into an inflammatory exudate

Inflammation, 1996

The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental ... more The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental exudate were compared for their ability to release superoxide anion (O 2−) and for their fatty acid composition, determined by capillary gaschromatography. The basal O 2− release and the phorbol myristate acetate (PMA)-induced O 2− release were not significantly different in the two neutrophil populations, while in response to formyl-methionyl-leucyl-phenylalanine (fMLP) the exudate cells showed an activity that was two fold higher than that of blood cells. The most significant changes of fatty acid composition of exudate versus blood cells were the following: i) increase of C16∶0 (palmitic acid) from 21.3±1.2% to 23.5±1.3% (+ 10.2%) of total fatty acids (p<0.001), ii) increase of C18:2 (linoleic acid) from 9.3±1.7% to 11.0±2.1% (+18.3%) (p=0.005), iii) decrease of C20∶4 (arachidonic acid) from 12.8±1.6% to 10.6±1.2% (−17.3%) (p<0.001), whereas C18∶1 (oleic acid) did not change. The total content of saturated or unsaturated fatty acids did not change. In exudate cells, a strong negative correlation was found between palmitic acid content and O 2− release in response to both fMLP and PMA (r=-0.52,p< 0.02 andr=−0.49,p<0.05, respectively) whereas arachidonic acid correlated positively, but weakly, with O 2−(r=0.40,p=0.07 andr=0.47,p=0.05, with fMLP and PMA as stimulants respectively). A positive correlation was also found between the arachidonic acid content of blood cells and the number of cells that migrated into the inflammatory exudate. These results indicate that the process of extravasation from blood into the exudate causes specific and consistent modifications of the fatty acid composition of neutrophils and suggest that these modifications have a role in the activation and the regulation of the O 2− forming system.

Research paper thumbnail of Membrane polyunsaturated fatty acids and lithium-sodium countertransport in human erythrocytes

Research paper thumbnail of Effects of linoleic acid supplementation on blood pressure and kinetics of red cell sodium transport

Journal of Hypertension, 1991

Research paper thumbnail of Severe impairment of antioxidant system in human hepatoma

Research paper thumbnail of Prognostic score in liver cirrhosis developed using the Cox's proportional hazard regression model

La Ricerca in clinica e in laboratorio

In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, ... more In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, 36 of these variables were statistically analyzed in 151 patients followed up for 8 years. The 'survival time' was taken as the reference variable. In a first step we analyzed by log-rank test and by Cox's proportional hazard regression model the data of 98 patients (study group), obtaining 7 prognostically significant variables (age, leukocytes, calcium, potassium, globulins, cholesterol and previous diagnosis). From the regression coefficients of these variables, a risk score was obtained for each patient. To validate the prognostic value of this score, we computed it, using the same coefficients obtained in the study group, in 53 subsequently examined patients (control group) showing that the prognostic score allows the classification of these patients in 3 risk classes with different observed survival times.

Research paper thumbnail of Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma

Cancer, 1985

To investigate the diagnostic and prognostic value of several biochemical tests in primary liver ... more To investigate the diagnostic and prognostic value of several biochemical tests in primary liver tumors, the authors studied 36 cases (4 cholangiocarcinomas and 32 hepatocellular carcinomas, 10 of which were associated with cirrhosis) and 47 cases of liver cirrhosis, all with morphologically proven diagnosis. Serum copper (SCu) and plasma fibrinogen (PF) appeared the most useful tests in differential diagnosis between tumors and cirrhosis. In liver tumors, mean SCu level was 200.50, standard deviation (SD) 47.17 pg/dl (121.40, SD 25.90 pg/dl in cirrhosis; P < 0.001). PF level was 461.78, S D 151.25 mg/dl in tumors (275.30 SD, 124.40 mg/dl in cirrhosis; P < 0.001). SCu had a good sensitivity (0.80) and a high specificity (0.92) at a cutoff value of 160 pgldl; when the cutoff level was raised to 170 pg/ dl, the specificity increased to 1, with a sensitivity of 0.77. The combination of SCu and P F improved the diagnostic value slightly. Moreover, with an estimated frequency of tumor in cirrhosis of lo%, SCu had a positive predictive value of I (cutoff, 170 pg/dl) and a negative predictive value of 0.97. In nine patients SCu levels decreased after surgical removal of tumor; five other patients, sequentially studied, showed an increase of SCu level that correlated with the progression of the disease. Finally, patients with longer survival had a lower SCu level. These findings suggest that SCu level may be used as a screening test for early detection of neoplastic degeneration, and it is correlated with the extension of tumor mass.

Research paper thumbnail of Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa

Hepatology, 1997

The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated vi... more The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT) normalization. Of the 50 untreated patients, 30 (60%) cleared HBeAg, but only 21 (42%) normalized ALT after HBeAg loss. Compared with the untreated patients, IFN-treated patients had similar cumulative rates of HBeAg clearance (P = .48), but higher rates of ALT normalization (P = .016) and of HBsAg loss (P = .028). During follow-up, liver-related death occurred in 8 treated patients, caused by liver failure in 5 and hepatocellular carcinoma (HCC) in 3; all 8 had continued to be HBeAg-positive with elevated ALT. None of the treated patients undergoing remission developed liver-related complications. At univariate analysis, life expectancy was longer in treated patients showing sustained remission than in those who did not (5-year survival: 100% vs. 81%; P = .048). Fourteen untreated patients died (from liver failure in 10 and HCC in 4); all but 3 had continued to be HBeAg-positive with elevated ALT. Cox&#39;s model identified age and ALT normalization as the only significant predictors of survival. In conclusion, in patients with HBeAg-positive compensated cirrhosis, virological and biochemical remission following IFN therapy is associated with improved survival.

Research paper thumbnail of Infective endocarditis with lung and systemic embolization in an injection drug user

European Heart Journal, 2006

Research paper thumbnail of Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid

Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2001

Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-indep... more Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H 1 -receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives. Patients and methods A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms. Results MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P , 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P , 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P , 0.001, and 20 days, P , 0.001, respectively). Finally, a low incidence of adverse events was observed in this study. Conclusion The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

Research paper thumbnail of Ham-positive Red Cells Induced In vitro by N-Acetylcysteine or D-Penicillamine

British Journal of Haematology, 1968

Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become... more Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become sensitive to lysis by acidified normal human serum, i.e. become PNH-like cells and give a positive Ham test. At the same time the cells lose some of their acetylcholinesterase activity. Substances active in this way share a common chemical grouping : HS-C-CH-NH.

Research paper thumbnail of Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile

Research paper thumbnail of Controlled Comparison of Ketanserin and Nifedipine in Raynaud's Phenomenon

Angiology, 1989

Twenty-eight patients suffering from either primary or secondary Raynaud&#39;s phenomenon wer... more Twenty-eight patients suffering from either primary or secondary Raynaud&#39;s phenomenon were treated with nifedipine and ketanserin. Each patient was treated with one of the two drugs administered after an adequate washout period. Furthermore each patient was submitted before and after treatment with each drug to computerized digital thermometry to evaluate the therapeutic response. The data obtained during the intake of the two drugs at zero, five, and twenty-three minutes were compared with thermometry-relevant baseline data at the same periods. Ketanserin proved to be useful in the treatment of Raynaud&#39;s phenomenon and statistically significantly superior (alpha less than 0.05) with respect to nifedipine in the thermometric controls and also in the subjective evaluation of the patients (p less than 0.02). In this study nifedipine did not show particular efficacy. Furthermore only 2 patients had to discontinue treatment with ketanserin, whereas 8 had to discontinue treatment with nifedipine (p less than 0.001).

Research paper thumbnail of Nickel sulphate, food additives and seronegative arthritis: is there any relationship?. Nickel sulphates are triggers or aggravating factors for seronegative arthritis

Allergy, 2003

Seronegative spondilo-arthropathies are characterized by particular clinical features such as sac... more Seronegative spondilo-arthropathies are characterized by particular clinical features such as sacroileitis, spondylitis and asymmetric peripheral arthritis mainly involving the lower limbs and negative rheumatoid factor. In most cases, they are associated with the HLA class I antigen B 27 (1). We have recently reported that in few selected cases of seronegative arthritis, articular symptoms may be triggered by food antigens (2). Therefore, as a complement to the above study (2), we discuss here the association between food additives, other substances like nickel sulphate and seronegative spondilo-arthropathies. In this study, we have enrolled 88 subjects, 54 females and 18 males, with ages ranging from 12 to 60 years, affected by seronegative arthritis and with suspected food additive intolerance on the basis of an improvement of symptoms after a food additives-free diet.

Research paper thumbnail of Serum Folate Binding Capacity in Leukemias, Liver Diseases and Pregnancy

Acta Haematologica, 1979

Total and unsaturated folate binding capacity (TFBC, UFBC) have been measured in sera of selectiv... more Total and unsaturated folate binding capacity (TFBC, UFBC) have been measured in sera of selective groups of patients to study the role of cell turnover, cell necrosis and the effect of pregnancy in determining their concentrations in blood. The mean value of TFBC in 35 normal sera was 151 +/- (SD) 53 pg/ml with a saturation of 88%. The TFBC was raised in chronic granulocytic leukemia (CGL), in acute hepatitis, in cirrhosis, and in pregnancy (third trimester). The normal mean value of TFBC was found in chronic lymphocytic leukemia (CLL) and inthe first trimester of pregnancy. The mean UFBC in the normal sera was 19 +/- 18 pg/ml. In all the pathological conditions studied the mean UFBC was significantly greater than normal and it was particularly high in CGL (85 +/- 78 pg/ml).

Research paper thumbnail of Effect of Human Erythrocyte Stromata on Complement Activation

British Journal of Haematology, 1975

Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis i... more Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis in the sucrose test and enhancing lysis in the acidified-serum test. The same opposing effects are displayed by the exclusion peaks from Sephadex G-200 obtained from each stroma preparation, suggesting that the same factor could be responsible for both activities. Stromata and peaks also induce lysis of PNH-like cells in unacidified serum, indicating activation of complement through the alternate pathway. This is confirmed by immunoelectrophoretic observation. When serum previously activated through the alternate pathway is used in the sucrose test the amount of lysis is markedly reduced. This would indicate that the classical pathway activation can be controlled by the alternate pathway. The possible clinical significance of these factors in determining the haemolytic crisis in PNH patients is discussed.

Research paper thumbnail of Measurement of urinary hepcidin levels by SELDI-TOF-MS in HFE-hemochromatosis

Blood Cells, Molecules, and Diseases, 2008

Insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as th... more Insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as the key pathogenetic feature of HFE-related hereditary hemochromatosis (HH). There is a growing interest in measuring the hepcidin levels, which may improve the diagnosis, prognostic evaluation and clinical management of HH. Nevertheless, few investigative tools are available: an immunodot method for urinary hepcidin developed by a single centre (UCLA), not yet ready for large-scale diffusion, and mass spectrometry (MS) based assays, such as surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF-MS). The latter is well suited to small peptides like hepcidin, and can rapidly analyze crude samples with high throughput. This study measured urinary hepcidin levels by SELDI-TOF-MS in a large group of HH patients at diagnosis and during treatment, including both C282Y homozygous and C282Y/H63D compound heterozygotes. We used a protocol based on PBSIIc mass spectrometer and Normal Phase chips. Urinary samples from 30 control subjects were compared to those obtained from 80 HH patients (57 C282Y homozygotes, 23 C282Y/H63D compound heterozygotes). Eighteen C282Y homozygotes and 11 C282Y/H63D compound heterozygotes were analyzed at diagnosis, the remainder during maintenance phlebotomy. C282Y homozygotes either at diagnosis, or after phlebotomy had significantly lower urinary hepcidin levels than controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). C282Y/H63D compound heterozygotes had hepcidin levels at diagnosis higher than controls, while the hepcidin/ferritin ratio was significantly decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) suggesting inadequate hepcidin production. After phlebotomy, mean hepcidin levels in the compound heterozygotes were significantly lower than in controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Samples from 12 randomly selected control subjects were sent to UCLA for duplicate measurement by the immunodot method, yielding a significant correlation (rho=0.64; P=0.024). This study supports the use of SELDI-TOF-MS for measuring hepcidin levels in research and clinical applications. Our results in phlebotomized patients suggest that the depletion of iron stores may further exacerbate the HFE-related hepcidin defect.

Research paper thumbnail of Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene

Gastroenterology, 2002

Background & Aims: Although most patients with hereditary hemochromatosis are homozygous for a si... more Background & Aims: Although most patients with hereditary hemochromatosis are homozygous for a single mutation of the HFE gene on chromosome 6p, accumulating evidence indicates that the disease is genetically heterogeneous. Type 3 hemochromatosis, recently described in 4 families, is linked to mutations of the gene encoding transferrin receptor 2 on chromosome 7q22. Here we report data from a family carrying a new mutation of the transferrin receptor 2 gene. Methods: Detailed clinical and histopathologic documentation was available for most family members. The entire coding sequence and exon/intron boundaries of the transferrin receptor 2 gene were analyzed by direct sequencing. Results: A 12-nucieotide deletion in exon 16, causing the loss of 4 amino acids (AVAQ 594-597 del), was detected at the homozygous state in the 3 patients with histologically proven iron overload. The deletion segregated with the disease within the family and was not found in 100 healthy controls. Some clinical and pathologic characteristics, such as low penetrance in the premenopausal woman, and early iron deposition in periportal hepatocytes resembled those of classic, HFErelated hemochromatosis. Conclusions: Our data support the role of the transferrin receptor 2 gene in hemochromatosis type 3 as well as its critical involvement in the maintenance of iron homeostasis in humans. Abbreviations used in this paper: HH, hereditary hemochromatosis; TFR, transferrin receptor; UGT, uridine diphosphate glucuronosyltransferase.

Research paper thumbnail of Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn’s disease

Journal of Internal Medicine, 2009

Lunardi C, Bason C, Dolcino M, Navone R, ). Antiflagellin antibodies recognize the autoantigens T... more Lunardi C, Bason C, Dolcino M, Navone R, ). Antiflagellin antibodies recognize the autoantigens Toll-Like Receptor 5 and Pals 1-associated tight junction protein and induce monocytes activation and increased intestinal permeability in Crohn's disease. J Intern Med 2009; 265: 250-265.

Research paper thumbnail of STIMA DELLA PREVALENZA DELL'IPERTENSIONE ARTERIOSA E DI ALTRI FATTORI DI RISCHIO CARDIOVASCOLARE NELLA POPOLAZIONE GENERALE RESIDENTE NELL'ASL 22 DELLA REGIONE VENETO

Finanziamenti: lavori eseguiti per conto della Regione Veneto, Giunta regionale -Ricerca Sanitaria

Research paper thumbnail of Ischemic Colitis Sustained by Sickle Cell Trait in Young Adult Patient

The American Journal of Gastroenterology, 2005

TO THE EDITOR: A 44-yr-old Brazilian woman was admitted to our Unit on October 2002 for abdominal... more TO THE EDITOR: A 44-yr-old Brazilian woman was admitted to our Unit on October 2002 for abdominal pain. Abdominal examination revealed decreased bowel sounds without guarding or rigidity. ... To read this article in full you may need to log in, make a payment or gain ...

Research paper thumbnail of Changes of fatty acid composition and oxidative metabolism of human neutrophils migrating into an inflammatory exudate

Inflammation, 1996

The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental ... more The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental exudate were compared for their ability to release superoxide anion (O 2−) and for their fatty acid composition, determined by capillary gaschromatography. The basal O 2− release and the phorbol myristate acetate (PMA)-induced O 2− release were not significantly different in the two neutrophil populations, while in response to formyl-methionyl-leucyl-phenylalanine (fMLP) the exudate cells showed an activity that was two fold higher than that of blood cells. The most significant changes of fatty acid composition of exudate versus blood cells were the following: i) increase of C16∶0 (palmitic acid) from 21.3±1.2% to 23.5±1.3% (+ 10.2%) of total fatty acids (p<0.001), ii) increase of C18:2 (linoleic acid) from 9.3±1.7% to 11.0±2.1% (+18.3%) (p=0.005), iii) decrease of C20∶4 (arachidonic acid) from 12.8±1.6% to 10.6±1.2% (−17.3%) (p<0.001), whereas C18∶1 (oleic acid) did not change. The total content of saturated or unsaturated fatty acids did not change. In exudate cells, a strong negative correlation was found between palmitic acid content and O 2− release in response to both fMLP and PMA (r=-0.52,p< 0.02 andr=−0.49,p<0.05, respectively) whereas arachidonic acid correlated positively, but weakly, with O 2−(r=0.40,p=0.07 andr=0.47,p=0.05, with fMLP and PMA as stimulants respectively). A positive correlation was also found between the arachidonic acid content of blood cells and the number of cells that migrated into the inflammatory exudate. These results indicate that the process of extravasation from blood into the exudate causes specific and consistent modifications of the fatty acid composition of neutrophils and suggest that these modifications have a role in the activation and the regulation of the O 2− forming system.

Research paper thumbnail of Membrane polyunsaturated fatty acids and lithium-sodium countertransport in human erythrocytes

Research paper thumbnail of Effects of linoleic acid supplementation on blood pressure and kinetics of red cell sodium transport

Journal of Hypertension, 1991

Research paper thumbnail of Severe impairment of antioxidant system in human hepatoma

Research paper thumbnail of Prognostic score in liver cirrhosis developed using the Cox's proportional hazard regression model

La Ricerca in clinica e in laboratorio

In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, ... more In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, 36 of these variables were statistically analyzed in 151 patients followed up for 8 years. The 'survival time' was taken as the reference variable. In a first step we analyzed by log-rank test and by Cox's proportional hazard regression model the data of 98 patients (study group), obtaining 7 prognostically significant variables (age, leukocytes, calcium, potassium, globulins, cholesterol and previous diagnosis). From the regression coefficients of these variables, a risk score was obtained for each patient. To validate the prognostic value of this score, we computed it, using the same coefficients obtained in the study group, in 53 subsequently examined patients (control group) showing that the prognostic score allows the classification of these patients in 3 risk classes with different observed survival times.

Research paper thumbnail of Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma

Cancer, 1985

To investigate the diagnostic and prognostic value of several biochemical tests in primary liver ... more To investigate the diagnostic and prognostic value of several biochemical tests in primary liver tumors, the authors studied 36 cases (4 cholangiocarcinomas and 32 hepatocellular carcinomas, 10 of which were associated with cirrhosis) and 47 cases of liver cirrhosis, all with morphologically proven diagnosis. Serum copper (SCu) and plasma fibrinogen (PF) appeared the most useful tests in differential diagnosis between tumors and cirrhosis. In liver tumors, mean SCu level was 200.50, standard deviation (SD) 47.17 pg/dl (121.40, SD 25.90 pg/dl in cirrhosis; P < 0.001). PF level was 461.78, S D 151.25 mg/dl in tumors (275.30 SD, 124.40 mg/dl in cirrhosis; P < 0.001). SCu had a good sensitivity (0.80) and a high specificity (0.92) at a cutoff value of 160 pgldl; when the cutoff level was raised to 170 pg/ dl, the specificity increased to 1, with a sensitivity of 0.77. The combination of SCu and P F improved the diagnostic value slightly. Moreover, with an estimated frequency of tumor in cirrhosis of lo%, SCu had a positive predictive value of I (cutoff, 170 pg/dl) and a negative predictive value of 0.97. In nine patients SCu levels decreased after surgical removal of tumor; five other patients, sequentially studied, showed an increase of SCu level that correlated with the progression of the disease. Finally, patients with longer survival had a lower SCu level. These findings suggest that SCu level may be used as a screening test for early detection of neoplastic degeneration, and it is correlated with the extension of tumor mass.

Research paper thumbnail of Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa

Hepatology, 1997

The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated vi... more The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT) normalization. Of the 50 untreated patients, 30 (60%) cleared HBeAg, but only 21 (42%) normalized ALT after HBeAg loss. Compared with the untreated patients, IFN-treated patients had similar cumulative rates of HBeAg clearance (P = .48), but higher rates of ALT normalization (P = .016) and of HBsAg loss (P = .028). During follow-up, liver-related death occurred in 8 treated patients, caused by liver failure in 5 and hepatocellular carcinoma (HCC) in 3; all 8 had continued to be HBeAg-positive with elevated ALT. None of the treated patients undergoing remission developed liver-related complications. At univariate analysis, life expectancy was longer in treated patients showing sustained remission than in those who did not (5-year survival: 100% vs. 81%; P = .048). Fourteen untreated patients died (from liver failure in 10 and HCC in 4); all but 3 had continued to be HBeAg-positive with elevated ALT. Cox&#39;s model identified age and ALT normalization as the only significant predictors of survival. In conclusion, in patients with HBeAg-positive compensated cirrhosis, virological and biochemical remission following IFN therapy is associated with improved survival.

Research paper thumbnail of Infective endocarditis with lung and systemic embolization in an injection drug user

European Heart Journal, 2006

Research paper thumbnail of Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid

Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2001

Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-indep... more Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H 1 -receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives. Patients and methods A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms. Results MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P , 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P , 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P , 0.001, and 20 days, P , 0.001, respectively). Finally, a low incidence of adverse events was observed in this study. Conclusion The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

Research paper thumbnail of Ham-positive Red Cells Induced In vitro by N-Acetylcysteine or D-Penicillamine

British Journal of Haematology, 1968

Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become... more Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become sensitive to lysis by acidified normal human serum, i.e. become PNH-like cells and give a positive Ham test. At the same time the cells lose some of their acetylcholinesterase activity. Substances active in this way share a common chemical grouping : HS-C-CH-NH.

Research paper thumbnail of Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile

Research paper thumbnail of Controlled Comparison of Ketanserin and Nifedipine in Raynaud's Phenomenon

Angiology, 1989

Twenty-eight patients suffering from either primary or secondary Raynaud&#39;s phenomenon wer... more Twenty-eight patients suffering from either primary or secondary Raynaud&#39;s phenomenon were treated with nifedipine and ketanserin. Each patient was treated with one of the two drugs administered after an adequate washout period. Furthermore each patient was submitted before and after treatment with each drug to computerized digital thermometry to evaluate the therapeutic response. The data obtained during the intake of the two drugs at zero, five, and twenty-three minutes were compared with thermometry-relevant baseline data at the same periods. Ketanserin proved to be useful in the treatment of Raynaud&#39;s phenomenon and statistically significantly superior (alpha less than 0.05) with respect to nifedipine in the thermometric controls and also in the subjective evaluation of the patients (p less than 0.02). In this study nifedipine did not show particular efficacy. Furthermore only 2 patients had to discontinue treatment with ketanserin, whereas 8 had to discontinue treatment with nifedipine (p less than 0.001).

Research paper thumbnail of Nickel sulphate, food additives and seronegative arthritis: is there any relationship?. Nickel sulphates are triggers or aggravating factors for seronegative arthritis

Allergy, 2003

Seronegative spondilo-arthropathies are characterized by particular clinical features such as sac... more Seronegative spondilo-arthropathies are characterized by particular clinical features such as sacroileitis, spondylitis and asymmetric peripheral arthritis mainly involving the lower limbs and negative rheumatoid factor. In most cases, they are associated with the HLA class I antigen B 27 (1). We have recently reported that in few selected cases of seronegative arthritis, articular symptoms may be triggered by food antigens (2). Therefore, as a complement to the above study (2), we discuss here the association between food additives, other substances like nickel sulphate and seronegative spondilo-arthropathies. In this study, we have enrolled 88 subjects, 54 females and 18 males, with ages ranging from 12 to 60 years, affected by seronegative arthritis and with suspected food additive intolerance on the basis of an improvement of symptoms after a food additives-free diet.

Research paper thumbnail of Serum Folate Binding Capacity in Leukemias, Liver Diseases and Pregnancy

Acta Haematologica, 1979

Total and unsaturated folate binding capacity (TFBC, UFBC) have been measured in sera of selectiv... more Total and unsaturated folate binding capacity (TFBC, UFBC) have been measured in sera of selective groups of patients to study the role of cell turnover, cell necrosis and the effect of pregnancy in determining their concentrations in blood. The mean value of TFBC in 35 normal sera was 151 +/- (SD) 53 pg/ml with a saturation of 88%. The TFBC was raised in chronic granulocytic leukemia (CGL), in acute hepatitis, in cirrhosis, and in pregnancy (third trimester). The normal mean value of TFBC was found in chronic lymphocytic leukemia (CLL) and inthe first trimester of pregnancy. The mean UFBC in the normal sera was 19 +/- 18 pg/ml. In all the pathological conditions studied the mean UFBC was significantly greater than normal and it was particularly high in CGL (85 +/- 78 pg/ml).

Research paper thumbnail of Effect of Human Erythrocyte Stromata on Complement Activation

British Journal of Haematology, 1975

Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis i... more Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis in the sucrose test and enhancing lysis in the acidified-serum test. The same opposing effects are displayed by the exclusion peaks from Sephadex G-200 obtained from each stroma preparation, suggesting that the same factor could be responsible for both activities. Stromata and peaks also induce lysis of PNH-like cells in unacidified serum, indicating activation of complement through the alternate pathway. This is confirmed by immunoelectrophoretic observation. When serum previously activated through the alternate pathway is used in the sucrose test the amount of lysis is markedly reduced. This would indicate that the classical pathway activation can be controlled by the alternate pathway. The possible clinical significance of these factors in determining the haemolytic crisis in PNH patients is discussed.

Research paper thumbnail of Measurement of urinary hepcidin levels by SELDI-TOF-MS in HFE-hemochromatosis

Blood Cells, Molecules, and Diseases, 2008

Insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as th... more Insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as the key pathogenetic feature of HFE-related hereditary hemochromatosis (HH). There is a growing interest in measuring the hepcidin levels, which may improve the diagnosis, prognostic evaluation and clinical management of HH. Nevertheless, few investigative tools are available: an immunodot method for urinary hepcidin developed by a single centre (UCLA), not yet ready for large-scale diffusion, and mass spectrometry (MS) based assays, such as surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF-MS). The latter is well suited to small peptides like hepcidin, and can rapidly analyze crude samples with high throughput. This study measured urinary hepcidin levels by SELDI-TOF-MS in a large group of HH patients at diagnosis and during treatment, including both C282Y homozygous and C282Y/H63D compound heterozygotes. We used a protocol based on PBSIIc mass spectrometer and Normal Phase chips. Urinary samples from 30 control subjects were compared to those obtained from 80 HH patients (57 C282Y homozygotes, 23 C282Y/H63D compound heterozygotes). Eighteen C282Y homozygotes and 11 C282Y/H63D compound heterozygotes were analyzed at diagnosis, the remainder during maintenance phlebotomy. C282Y homozygotes either at diagnosis, or after phlebotomy had significantly lower urinary hepcidin levels than controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). C282Y/H63D compound heterozygotes had hepcidin levels at diagnosis higher than controls, while the hepcidin/ferritin ratio was significantly decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) suggesting inadequate hepcidin production. After phlebotomy, mean hepcidin levels in the compound heterozygotes were significantly lower than in controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Samples from 12 randomly selected control subjects were sent to UCLA for duplicate measurement by the immunodot method, yielding a significant correlation (rho=0.64; P=0.024). This study supports the use of SELDI-TOF-MS for measuring hepcidin levels in research and clinical applications. Our results in phlebotomized patients suggest that the depletion of iron stores may further exacerbate the HFE-related hepcidin defect.

Research paper thumbnail of Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene

Gastroenterology, 2002

Background & Aims: Although most patients with hereditary hemochromatosis are homozygous for a si... more Background & Aims: Although most patients with hereditary hemochromatosis are homozygous for a single mutation of the HFE gene on chromosome 6p, accumulating evidence indicates that the disease is genetically heterogeneous. Type 3 hemochromatosis, recently described in 4 families, is linked to mutations of the gene encoding transferrin receptor 2 on chromosome 7q22. Here we report data from a family carrying a new mutation of the transferrin receptor 2 gene. Methods: Detailed clinical and histopathologic documentation was available for most family members. The entire coding sequence and exon/intron boundaries of the transferrin receptor 2 gene were analyzed by direct sequencing. Results: A 12-nucieotide deletion in exon 16, causing the loss of 4 amino acids (AVAQ 594-597 del), was detected at the homozygous state in the 3 patients with histologically proven iron overload. The deletion segregated with the disease within the family and was not found in 100 healthy controls. Some clinical and pathologic characteristics, such as low penetrance in the premenopausal woman, and early iron deposition in periportal hepatocytes resembled those of classic, HFErelated hemochromatosis. Conclusions: Our data support the role of the transferrin receptor 2 gene in hemochromatosis type 3 as well as its critical involvement in the maintenance of iron homeostasis in humans. Abbreviations used in this paper: HH, hereditary hemochromatosis; TFR, transferrin receptor; UGT, uridine diphosphate glucuronosyltransferase.