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Biomedical subjects

C Barbera

Publications and source records attributed to C Barbera.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.

Adult↗
PubMed2005

Therapeutic ERCP in paediatric patients.

BACKGROUND: Major limitations of endoscopic retrograde cholangiopancreatography in paediatric populations are a low incidence of biliopancreatic disease among children, the equipment dimensions (size of endoscopes and devices) and the increasing role of MR-cholangiopancreatography in the field of diagnostic indications. Aim of this study was to evaluate the diagnostic and therapeutic yields of endoscopic retrograde cholangiopancreatography for biliopancreatic diseases in a paediatric population. METHODS: Between 1996 and 2002, 48 endoscopic retrograde cholangiopancreatographies were performed in 38 children aged 4 weeks to 17 years as part of the diagnostic evaluation for suspected pancreatic or biliary tract disease. Endoscopic retrograde cholangiopancreatography was carried out under general anaesthesia, using prototype paediatric duodenoscopes or standard duodenoscopes in children younger or older than 18 months, respectively. RESULTS: The indications to perform endoscopic retrograde cholangiopancreatography were common bile duct stones (14 children), biliopancreatic abnormalities (8), primary sclerosing cholangitis (2), Wirsung disruption (1), biliary leakage (1), cholestasis (4) and pancreatitis (8). Cannulation was successful in all patients but one. Sphincterotomy together with stone extraction or stent insertion was performed in 30/38 patients. Immediate complications were mild and treated conservatively. CONCLUSIONS: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography can be used safely and effectively in the management of biliopancreatic diseases in childhood as well. Indications, endoscopic techniques and complications are similar to those reported for adult patients.

Acute Disease↗
PubMed2005

Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders.

BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking in children with hepatitis C and the long-term safety and efficacy of interferon is unknown. This study describes the outcome of hepatitis C in 43 children enrolled in an open-label interferon trial, and were followed up to 66 months after stopping treatment. PATIENTS AND METHODS: All patients received interferon alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received 3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children discontinued interferon for adverse events and three were not compliant to treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12 months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6 months), response was maintained; two non-responders cleared viremia, while a young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy withdrawal are the major limitations in the interpretation of our results. Nevertheless, our data, suggesting that response to interferon in children with hepatitis C is genotype-related and stable, agree with the results of large studies in adults. The outcome in non-responders was variable, including persistence of viremia and mild-moderate cytolysis (most cases), progression to cirrhosis, or eventual sustained viremia clearance.

Adolescent↗
PubMed2005

Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome.

BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.

Adolescent↗
PubMed2002

Acute pancreatitis in children. An Italian multicentre study.

AIM: To evaluate the clinical, morphological and aetiological aspects of acute pancreatitis in children in Italy. PATIENTS: The hospital records of 50 consecutive patients with acute pancreatitis observed in 5 Italian Pediatric Departments were reviewed. RESULTS: A total of 25 males and 25 females (median age 10.5 years, range 2-17) were studied. Of these patients, 48 (96%) had abdominal pain. The pancreatitis was associated with biliary disease in 10 patients (20%); it was due to viral infection in 6 patients (12%), pancreatic duct abnormalities in 4 (8%, familial chronic pancreatitis in 3 (6%), trauma in 5 (10%) and other causes in 5 (10%); the pancreatitis was of unknown origin in 17 patients (34%). Previous attacks of the disease had occurred in 14 patients. A diagnosis of mild pancreatitis was made in 41 patients (82%) and of severe disease in 9 (18%). One patient with severe pancreatitis died from multiorgan failure. Patients with severe pancreatitis had significantly higher serum concentrations of C-reactive protein than patients with mild pancreatitis. Hospital stay was similar for patients with the mild form and those with the severe form of the disease. CONCLUSIONS: In Italian children, acute pancreatitis is of unknown origin in about one-third of the children and is recurrent in 28% of the cases. The disease is severe in 18% of the cases.

Acute Disease↗
PubMed2002

Azathioprine in paediatric inflammatory bowel disease: an Italian multicentre survey.

AIM: To assess the efficacy and safety of azathioprine in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: One hundred and twenty-three Italian children treated with azathioprine were studied retrospectively. The treatment duration and causes of its discontinuation, side-effects and variation in corticosteroid dose were assessed. RESULTS: The mean age at inflammatory bowel disease diagnosis was 9.8 +/- 3.6 years, and at the start of azathioprine therapy 11.8 +/- 4.3 years. The mean duration of treatment was 19 +/- 16 months. Fifty patients (41%) stopped treatment due to surgery (12%), prolonged remission (11%), non-response (7%), severe side-effects (7%) and poor compliance (3%). Of the 73 patients (59%) remaining on azathioprine, 11 had never been treated with corticosteroids, 27 were able to stop them and 35 were still on a very low daily dose (91% < 0.3 mg/kg). The difference in the daily corticosteroid dose between the beginning of azathioprine treatment (1 +/- 0.6 mg/kg) and the conclusion of the study (0.18 +/- 0.16 mg/kg) was statistically significant. Side-effects were recorded in 48 of the 123 patients (39%), but only eight required discontinuation of azathioprine. CONCLUSIONS: Azathioprine was efficacious in 70% of patients, but ineffective in 20% and induced severe toxicity in 7%. Corticosteroids were stopped or markedly reduced in 62% of patients, but they were never given in 9%.

Adolescent↗
PubMed2002

IL-15 in human visceral leishmaniasis caused by Leishmania infantum.

Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-gamma (IFN-gamma). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-gamma and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-gamma, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.

Adult↗
PubMed2001

Hepatitis B virus infection in native versus immigrant or adopted children in Italy following the compulsory vaccination.

BACKGROUND: Compulsory vaccination of children against hepatitis B virus (HBV) infection was introduced in Italy in 1991. PATIENTS AND METHODS: To evaluate the current importance of pediatric HBV infection, we studied 359 HBsAg-positive children admitted to 16 centers in Italy from 1991 to 1998. 185 patients were natives of Italy and 174 (39 immigrants and 135 adopted) came from highly endemic countries (eastern Europe: 60.9%, Asia: 16.7%, Africa: 14.9% and Central and South America: 5.7%). RESULTS: Transaminase Levels were moderately altered in both Italian (mean 134 UI/L) and foreign children (mean 168 UI/L). In total, 77% of ItaLian children and 88% of foreign children tested HBeAg positive. High transaminase levels and HBeAg positivity were more frequent in adopted children. Follow-up of 317 patients showed that the incidence of HBeAg/anti-HBe serum conversion was similar in all cohorts, but in adopted children it occurred at an earlier age and was associated with HBsAg clearance in 5%. CONCLUSION: HBV is not frequent in Italian children today, but it is common among children coming from highly endemic areas. The vaccination of nonimmune native populations must be strongly recommended.

Adolescent↗
PubMed2001

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line.

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA accumulation indicates that the inhibiting activity is mainly post-transcriptional. CMTs were unable to modulate TNF-alpha and IL-10 synthesis and they were not effective in modifying the transcription of relative mRNA in J774 macrophages. On the contrary, IL-12 mRNA expression was significantly increased by CMT-1 and CMT-8 with LPS activation. Since IL-12 protein secretion was inhibited by CMTs, these compounds interfere in the blocking of post-transcriptional events. The studies on cell viability showed that various CMTs induced a dose-dependent decrease in J774 macrophage viability. The cytotoxic activity was present even though NO production was inhibited by CMTs. These compounds appear to be able to activate apoptosis in aNO-independent way. Altogether, these results indicate that CMTs can exert anti-inflammatory effects by inhibiting NO synthesis, and they are able to modify cell viability by exerting a strong apoptotic activity.

Acridine Orange↗
PubMed2001

Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines.

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar to that shown by doxycycline. On the contrary, CMT-1 and CMT-8 were very effective as programmed cell death inducing agents. The apoptotic pathway activated by these compounds involved the activation of caspases, especially caspase-9 and, for CMT-1, also the activation of FAS: Interestingly CMT-8, but not CMT-1, was able to induce apoptosis in multidrug resistant HL60R and in Fas-ligand resistant HUT78B1 cell lines. These properties, together with others previously described (e.g. anti-metastatic and anti-osteolytic activities), suggest that CMT-8 may have important applications in the clinical management of cancer. The comparative analysis of structure-activity relationship of CMT-8 and doxycycline suggests that the C-5 hydroxy moiety may play an important role in conferring activity in multidrug resistant cells. These findings appear to support the hypothesis that CMT-8 may represent an interesting lead for the development of a new class of potent apoptosis inducer agents active in multidrug resistant and Fas-ligand resistant malignancies.

Anti-Bacterial Agents↗
PubMed2001

The acute phase response in Sicilian patients with boutonneuse fever admitted to hospitals in Palermo, 1992-1997.

OBJECTIVES: To study the modifications of some components of the acute phase response (APR) in Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. METHODS: Sera from 500 Sicilian patients with confirmed BF were studied at the time of diagnosis and every week after treatment, and after recovery for the presence of various inflammatory mediators. Tumour necrosis factor alpha (TNFalpha), interleukin(IL)-6, IL-1alpha, IL-8, soluble TNF receptors (sTNF-R) and sIL-6R were assayed by commercially ELISA kits. C3, C4, factor B, C-reactive protein (CRP), fibrinogen, ceruloplasmin (Cp) and alpha(1)-antitrypsin (AAT) were assayed by a rate nephelometry. RESULTS: Interferon gamma (IFNgamma), IL-6, TNFalpha, and IL-10 cytokines were significantly modified, whereas IL-1 and IL-8 were not detectable in the blood in any phase of infection. sTNF-RI, sTNF-RII and sIL-6 were significantly increased in the first 2 weeks of infection, but sTNF-R levels were not related to the plasma levels of TNFalpha, whereas sIL-6 was directly related to serum IL-6 concentrations. C3, C4, factor B and CRP were significantly increased in the first 2 weeks of infection, but afterwards returned to the normal range, even though CRP was still high in the third week and C3 persisted high after the fourth week. Fibrinogen was high only in the first week in relation to the injury to the endothelial cells (ECs). The anti-inflammatory proteins, Cp and AAT, were extremely high in the first 2 weeks of infection acting as a buffer of APR activation. CONCLUSIONS: These results suggest that R. conorii is able to elicit, after invasion and proliferation in the ECs, the activation of APR. Further work is required to establish if active inhibitory mechanisms are operating during APR, or if there is a spontaneous decay in the initiation events.

Acute-Phase Proteins↗
PubMed2001

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.

Adolescent↗
PubMed2000

Tension-free hernia repair is associated with an increase in inflammatory response markers against the mesh.

BACKGROUND: The purpose of this study was to evaluate the involvement of inflammatory mediators in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia repair (BH). METHODS: Thirty patients male with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent LH or BH. Peripheral venous bloods samples were collected 24 hours prior to surgery and then 6, 24, 48 and 168 hours postoperatively. RESULTS: We present evidences that LH patients showed a higher increased serum level of fibrinogen, C-reactive protein, alpha-1-antitrypsin, and interleukin-6 than BH patients. Postoperative visual analogue scales for pain were reduced on mobilization for patients undergoing LH compared with BH. Neutrophils were significantly increased only in LH compared with baseline. Ceruloplasmin, transferrin, and albumin levels were unmodified after BH or LH. CONCLUSIONS: In conclusion our data show that although LH induces less pain and more rapid postoperative recovery, it is associated with an higher inflammatory response compared with BH, likely due to polypropylene mesh.

Adult↗
PubMed2000

Interleukin-12 in human boutonneuse fever caused by Rickettsia conorii.

Interleukin (IL)-12 contributes to the resistance against a number of intracellular pathogens. We examined the potential biological role of IL-12 by studying peripheral blood mononuclear cells (PBMC), its production and its effect on cytokine synthesis in 20 Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. Data indicate that PBMC from acute BF patients were able to produce IL-12 in response to in vitro stimulation with rickettsial antigen (Ag): this production was higher than that detected in healed patients. Monocytes were the main source of IL-12 by PBMC from BF patients. IL-12 secretion by in vitro Ag-stimulated PBMC from BF patients was potentiated by recombinant interferon gamma (IFN-gamma) or anti-IL-10 monoclonal antibodies (MoAbs). Furthermore, the treatment with anti-IL-12 MoAbs reduced the IFN-gamma synthesis. These results indicate that treatment of PBMC from acute BF patients with IL-12 shifted the response toward a Th1-type cytokine response. Furthermore, IL-12 and IFN-gamma are interdependent and they may be associated with the immunity against rickettsias.

Boutonneuse Fever↗
PubMed2000

Long term effect of alpha interferon in children with chronic hepatitis B.

BACKGROUND/AIMS: The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha. PATIENTS: A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months). RESULTS: Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients. CONCLUSIONS: After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not differ from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient.

Adolescent↗
PubMed1999

Jagged-1 mutation analysis in Italian Alagille syndrome patients.

Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged-1 (JAG1) gene, which encodes a ligand of Notch, has recently been found mutated in AGS. In this study, mutation analysis of the JAG1 gene performed on 20 Italian AGS patients led to the identification of 15 different JAG1 mutations, including a large deletion of the 20p12 region, six frameshift, three nonsense, three splice-site, and two missense mutations. The two novel missense mutations were clustered in the 5' region, while the remaining mutations were scattered throughout the gene. The spectrum of mutations in Italian patients was similar to that previously reported. We also studied in detail a complex splice site mutation, 3332dupl8bp, which was shown to lead to an abnormal JAG1 mRNA, resulting in a premature stop codon. With the exception of the missense mutations, the majority of the JAG1 mutations are therefore likely to produce truncated proteins. Since the phenotype of the patient with a complete deletion of the JAG1 gene is indistinguishable from that of patients with intragenic mutations, our study further supports the hypothesis that haploinsufficiency is the most common mechanism involved in AGS pathogenesis. Furthermore, our data confirmed the absence of a correlation between the genotype of the JAG1 gene and the AGS phenotype.

Alagille Syndrome↗
PubMed1999

Differential up-regulation of circulating soluble selectins and endothelial adhesion molecules in Sicilian patients with Boutonneuse fever.

In 150 patients with Boutonneuse fever (BF), caused by Rickettsia conorii, we studied the plasma levels of soluble L-selectin (sL-selectin), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in various phases of disease to clarify their role in disease evolution. Results indicate that during the acute phase of BF there is a significant increase in the serum levels of sL-selectin, sE-selectin, sVCAM-1 and sICAM-1. sL-selectin and sVCAM-1 returned to normal levels in the third week of disease, whereas sE-selectin and sICAM-1 persisted at significantly high levels even after the third week. The secretion of these soluble CAMs in BF is mainly the result of leucocyte expression and endothelial cell activation, but secretion also appears to mediate anti-inflammatory activities, moderating leucocyte adhesion and reducing in particular lymphocyte and monocyte infiltration. Only sL-selectin serum levels were found to correlate with the acute phase of infection characterized by fever.

Adult↗