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Biomedical subjects

Antonio Carroccio

Publications and source records attributed to Antonio Carroccio.

29 records · Page 2Linked to original sources

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.

Adult↗

Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children.

BACKGROUND: Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying "organic" causes of chronic diarrhea in consecutive adults and children. METHODS: We consecutively enrolled 70 adult patients (30 males, 40 females; median age, 35 years) and 50 children (20 males, 30 females; median age, 3.5 years) with chronic diarrhea of unknown origin. All patients underwent a complete work-up to identify the causes of chronic diarrhea. FC was measured by ELISA. RESULTS: In adult patients, FC showed 64% sensitivity and 80% specificity with 70% positive and 74% negative predictive values for organic causes. False-positive results (8 of 40 cases) were associated with the use of aspirin (3 cases) or nonsteroidal antiinflammatory drugs (1 case) and with the presence of concomitant liver cirrhosis (3 cases). False-negative results mainly included patients suffering from celiac disease (5 cases). Patients with IBD (9 cases) were identified with 100% sensitivity and 95% specificity. In pediatric patients, sensitivity was 70%, specificity was 93%, and positive and negative predictive values were 96% and 56%. False-negative results (11 of 35 cases) were associated mainly with celiac disease (6 cases) or intestinal giardiasis (2 cases). CONCLUSIONS: FC assay is an accurate marker of IBD in both children and adult patients. In adults, false negatives occur (e.g., in celiac disease) and false-positive results are seen in cirrhosis or users of nonsteroidal antiinflammatory drugs. Diagnostic accuracy is higher in children.

Adolescent↗

Leucocyte interferon-alpha for patients with chronic hepatitis C intolerant to other alpha-interferons.

BACKGROUND: Alpha-interferon (alpha-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of alpha-IFN or prolonged therapy have increased the number of cases of intolerance. STUDY DESIGN: In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNalpha) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNalpha. All patients were treated for 6 months and followed-up for an additional 6 months.End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations. RESULTS: Five patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders. CONCLUSIONS: This study shows that leucocyte IFNalpha at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNalpha, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.

Antiviral Agents↗

Risk of non-Hodgkin lymphoma in celiac disease.

CONTEXT: Celiac disease is one of the most common lifelong disorders. Non-Hodgkin lymphoma is a possible complication of celiac disease and may lead to a large portion of lymphoma cases. OBJECTIVE: To quantify the risk for developing non-Hodgkin lymphoma of any primary site associated with celiac disease. DESIGN AND SETTING: Multicenter, case-control study conducted between January 1996 and December 1999 throughout Italy. PATIENTS: Cases were older than 20 years (median, 57; range, 20-92 years) with non-Hodgkin lymphoma of any primary site and histological type and were recruited at the time of the diagnosis. Controls were healthy adults (2739 men and 2981 women) from the general population. MAIN OUTCOME MEASURE: Positive test result for class A serum antiendomysial antibody. RESULTS: Celiac disease was diagnosed in 6 (0.92%) of 653 patients with lymphoma. Of the 6 cases, 3 were of B-cell and 3 were of T-cell origin. Four of 6 cases had lymphoma primarily located in the gut. In the control group, 24 (0.42%) had celiac disease. The odds ratio (adjusted for age and sex) for non-Hodgkin lymphoma of any primary site associated with celiac disease was 3.1 (95% confidence interval [CI], 1.3-7.6), 16.9 (95% CI, 7.4-38.7) for gut lymphoma, and 19.2 (95% CI, 7.9-46.6) for T-cell lymphoma, respectively. The risk for non-Hodgkin lymphoma for the overall population, which was adjusted for age and sex, was 0.63% (95% CI, - 0.12% to 1.37%). CONCLUSION: Celiac disease is associated with an increased risk for non-Hodgkin lymphoma, especially of T-cell type and primarily localized in the gut. However, the association does not represent a great enough risk to justify early mass screening for celiac disease.

Adult↗

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report.

Increase in the number of blood platelets to over 1,000,000/mm3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1,400,000/mm3). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tracts. She had never suffered from gastrointestinal problems and had no family history of gastroenterological diseases. Oesophagogastroduodenoscopy and histology of the gastric and duodenal mucosa evidenced atrophic gastritis and an adenomatous polyp. The duodenal mucosa showed total villous atrophy, suggesting the diagnosis of coeliac disease. Antiendomysial IgA and anti-transglutaminase IgA antibodies were also positive. Colonoscopy was negative. An ultrasound examination of the abdomen was normal, and the spleen was within the normal range. A peripheral blood smear showed no alterations in erythrocyte morphology typical of hyposplenism due to coeliac disease. The platelet count decreased rapidly after blood transfusions, when both serum iron and ferritin levels were still below normal limits. Furthermore, we observed a significant inverse correlation between the platelet count and haemoglobin concentration (r = -0.94, P < 0.003). Platelet count and red blood cell count normalized after 2 months of a gluten-free diet; the haemoglobin concentration was also normal at this time. After 1 year of following a gluten-free diet, the patient remained well and had no complaints. There were no gastrointestinal disturbances. All haematological parameters were within normal limits. Intestinal biopsies showed normal villi and crypts without inflammatory infiltration of the lamina propria. This case shows that the association of haematological signs--extreme thrombocytosis and severe anaemia--considered in an elderly patient to be typical of myeloproliferative disorders or neoplastic conditions can be due to coeliac disease; thus, coeliac disease must also be considered among the possible diagnoses.

Aged↗

Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: a prospective study.

BACKGROUND: Most studies of anti-transglutaminase (anti-tTG) assays have considered preselected groups of patients. This study compared the sensitivity, specificity, and predictive value of an immunofluorescence method for anti-endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients investigated for suspected celiac disease (CD). METHODS: We studied 207 consecutive patients (99 men, 108 women; age range, 17-84 years) who underwent intestinal biopsy for suspected CD. Patients presented with one or more of the following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits, constipation, pain in the joints, and dermatitis. At entry to the study, an intestinal biopsy was performed and a serum sample was taken for IgA EmAs, anti-gp-tTG, and anti-h-tTG. RESULTS: Intestinal histology showed that 24 patients had partial or total villous atrophy; in these patients the diagnosis of CD was confirmed by follow-up. The remaining 183 patients had villous/crypt ratios that were within our laboratory's reference values and were considered controls. Serum EmAs, anti-gp-tTG, and anti-h-tTG were positive in all 24 CD patients; in the control group, none were positive for serum EmAs, but 15 of 183 (8.2%) were positive for anti-gp-tTG, and 6 of 183 (3.3%) were positive for anti-h-tTG. Sensitivity was 100% for all assays, whereas specificity was 100% for the EmA, 92% for the anti-gp-tTG, and 97% for the anti-h-tTG assay. The negative predictive value was 100% for all assays; the positive predictive value was 100% for the EmA, 80% [95% confidence interval (CI), 65-95%] for the anti-h-tTG (P = 0.03 vs EmA) and 60% (95% CI, 44-76%) for the anti-gp-tTG assay (P = 0.0002 vs EmA). Areas (95% CIs) under the ROC curves were 0.987 (0.97-1.0) for anti-h-tTG and 0.965 (0.94-0.99) for anti-gp-tTG. Most of the patients testing false positive for anti-tTG had Crohn disease or chronic liver disease. CONCLUSIONS: Although both anti-tTG ELISAs showed optimum sensitivity, their lack of specificity yielded positive predictive values significantly lower than those for the EmA assay.

Adolescent↗

[Predictive value of serological tests in the diagnosis of celiac disease].

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.

Adolescent↗

Diagnosis of focal nodular hyperplasia. Role of imaging techniques.

Focal nodular hyperplasia (FNH) is a rare benign liver lesion which is difficult to differentiate from other benign liver pathologies and hepatocellular carcinoma. However, with appropriate new imaging techniques it is, at present, possible to diagnose this lesion with certainty thus avoiding invasive tests. Patient follow-up is also facilitated. It is often incidentally discovered during an abdominal ultrasound for other pathologies. Color power Doppler allows, in most cases, one to distinguish it from other focal liver lesions. However, in doubtful cases contrast-enhanced computed tomography and magnetic resonance imaging can help us to define the exact nature of the lesion. It is only occasionally necessary to perform an ultrasound-guided liver biopsy of the nodule and anyhow, once a correct diagnosis has been made, in most cases there is no indication for surgery. In spite of the contradictory results in the literature on the effects of oral contraceptives and pregnancy on the evolution of FNH, it now seems that they do not condition the appearance or the size of FNH and that in a woman with FNH pregnancy should not only be discouraged, but rather favored and closely monitored.

Biopsy↗

Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.

With the widespread use of ultrasonography (US) and computerized tomography (CT), the usefulness of alpha-fetoprotein assay in the diagnosis of hepatocellular carcinoma (HCC) has decreased. The aim of our study was to evaluate the best cut-off value for serum alpha-fetoprotein to discriminate between liver cirrhosis (LC) and HCC and the factors influencing levels in a Sicilian population. Three hundred and seventy-two patients with LC and 197 with HCC-associated LC were studied. The etiology was: HCV in 288 cases (77.4%) of LC and 147 cases (75%) of HCC; HBV in 31 cases (8.3%) of LC and 15 cases (7.6%) of HCC; HCV/HBV in 21 cases (5.6%) of LC and 6 cases (3.0%) of HCC; non-viral in 32 cases (8.6%) of LC and 29 cases (15%) of HCC. Hepatic function was estimated by the Child-Pugh's score; the TNM classification was used in HCC. The area under the ROC curve was 0.81 +/- 0.02; the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was 30 ng/ml. At this level sensitivity (SE) was 65%, specificity (SP) 89%, positive predictive value (PPV) 74% and negative predictive value (NPV) 79%. When the patients were divided at this cut-off point into two groups according to viral or non-viral etiology, PPV was 70% versus 94%, respectively (p < 0.05). In the non-viral diseases PPV reached 100% for AFP serum levels of 100 ng/ml, while in the viral diseases PPV was 100% when AFP was greater than 400 ng/ml. There were no significant differences in SE, SP or NPV between viral and non-viral liver diseases. Child's classes B and C were more frequent in HCC (chi 2 of MH 7.7, p < 0.0001). There was a correlation between AFP serum values and TNM classification (p < 0.02) and on multiple logistic regression AFP levels > 30 ng/ml correlated positively only with the TNM stage (p < 0.0001). In conclusion, the best cut-off value for serum AFP in our study population was 30 ng/ml, but at this level sensitivity was low. This cut-off value was more useful in detecting non-viral HCC, because PPV was significantly higher than in viral HCC; therefore, our data confirm that the usefulness of AFP in the diagnosis of HCC of viral etiology is limited, being more useful in HCC of non-viral etiology.

Aged↗