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O Perrella

Publications and source records attributed to O Perrella.

At least 19 recordsLinked to original sources
PubMed2006

Acute rejection after liver transplantation: Is there a specific immunological pattern?

The aim of the study was to assess various T-cell subsets and cytokine secretion patterns both in liver tissue and in the peripheral blood of 24 liver transplant patients to assess possible specific immunological involvement in early acute rejection episodes after liver transplantation. Particularly, we studied CD4+ CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine possible Th1-like immune responses and the immunomodulation expressed by Treg cells in acute liver rejection, respectively. As a control group we included patients transplanted without acute rejection. Early acute rejection within the first 4 weeks was proven histologically in 42% of patients. It was associated with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells was evident in patients with acute rejection (P < .001). Our data suggested that a preferential Th1-like immune mechanism operated in local fashion as characterized by a decreased presence in the liver and blood of Treg cells.

ADP-ribosyl Cyclase 1↗
PubMed2005

A clinical-morphological study on cholestatic presentation of nonalcoholic fatty liver disease.

To determine the association among the clinical, biochemical, and histological features of cholestasis, we analyzed all the relevant data of the patients recorded in our non-alcoholic fatty liver disease (NAFLD) database. We selected 20 NAFLD patients with abnormal transaminase levels, with both alkaline phosphatase >500 U/L and gamma-glutamyl transpeptidase >250 U/L. Their histological features were compared with those of a group of patients with NAFLD matched for sex, age, and body mass index and of a group of patients matched for sex, body mass index and histological NAFLD grading/staging. Cases and controls satisfied, on histology, the criteria for NASH. The presence of cholestasis in our patients was correlated with injury of the bile duct epithelium, characterized by cholangitis, swelling, variable bile duct loss, and bile stasis. Compared to NAFLD patients of similar age, sex, and body mass index, the cholestatic group had total and severe histological liver impairment. When we analyzed the group of patients histologically identified on the basis of identical stage and grade severity, we could not find any evidence of significant bile damage, compared to cases, despite the control group's significantly older age. NAFLD patients with biochemical cholestasis have a histological picture of bile damage; they have more advanced histological impairment than patients matched for age, sex and body mass index.

Aged↗
PubMed2004

Clinical presentation and prevalence of spontaneous bacterial peritonitis in patients with cryptogenic cirrhosis and features of metabolic syndrome.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis. The prevalence and clinical relevance that spontaneous bacterial peritonitis may have in complicating ascites due to NASH-related cirrhosis have yet to be defined. METHODS: Among 611 cases of cirrhosis-associated ascites, 45 patients with cryptogenic cirrhosis were retrospectively identified. Of these, 36 patients and a control group of subjects with viral- associated ascites were followed up and compared in a case control study. Information on the onset of ascites, with or without spontaneous bacterial peritonitis, history of risk factors for multimetabolic syndrome, and serological and ascitic laboratory data were compared between groups. RESULTS: Spontaneous bacterial peritonitis occurred significantly more often in patients with cryptogenic cirrhosis than in equally symptomatic viral controls. The prevalence of obesity, diabetes and spontaneous bacterial peritonitis was significantly higher in patients with cryptogenic cirrhosis. Although liver function was similar in both groups, cryptogenic cirrhosis patients had lower aminotransferase levels. Multivariate analysis identified diabetes, juvenile obesity and spontaneous bacterial peritonitis as independent factors associated with ascites due to cryptogenic cirrhosis. CONCLUSIONS: Features suggestive of NASH are more frequently observed in patients with ascites and cryptogenic cirrhosis than in age- and sex-matched ascitic patients with well-defined viral etiology. Ascites may be a presenting symptom of NASH-related cirrhosis, and affected patients have a twofold greater risk of spontaneous bacterial peritonitis.

Aged↗
PubMed2003

Low daily dosage of interferon for 1 year after HCV-related end-therapy response. A randomized-controlled study.

This randomized controlled study involved 236 1b genotype (121 males) naive patients with chronic hepatitis C. After a course of interferon (IFN)-alpha2b plus ribavirin for 6 or 12 months, 117 (49.5%) of the end-therapy responders were equally divided into two groups and were assigned to receive either low daily doses of IFN-alpha2b (1.5 MU) 'consolidation therapy' (59 patients) for 1 year or no further treatment (58 patients). At the end of the follow-up period (6 months), the number of sustained responders in the consolidation group (83%) was significantly higher than in the control group (37.9%). The predicting factors of both end-therapy response and sustained response were the classic ones and a lower GGT/ALT ratio (GGT: gamma-glutamyl transpeptidase; ALT: alanine aminotransferase). The strongest predictors of sustained response alone were consolidation therapy and the longer period on combined treatment (12 vs 6 months). Consolidation therapy was better tolerated than the previously prescribed combined therapy in terms of side effects. In conclusion, genotype 1b naive end-therapy responders to usual combined therapy, after a period of daily consolidation therapy with a low dosage of IFN without ribavirin, achieved a better rate of sustained response than the control group.

Adolescent↗
PubMed2001

Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.

BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Alanine Transaminase↗
PubMed2001

Transforming growth factor beta-1 and interferon-alpha in the AIDS dementia complex (ADC): possible relationship with cerebral viral load?

Mechanisms involved in the pathogenesis of the AIDS-dementia complex are still unclear. The dichotomy between a small number of HIV-infected cells in the brain and their marked dysfunction could be related to a cellular amplification and/or activation of cerebral viral load by several cytokines. This link between cytokines and viral load could play a role in the generation of the clinical dementia syndrome. We have studied cerebral levels of transforming growth factor-beta1 and interferon-alpha, both in the mild and severe AIDS-dementia complex and also compared these cytokines with HIV RNA load in patients with different degrees of dementia. Our data indicate that production of different cytokines characterized the expression of clinical dementia. In the mild AIDS-dementia complex, there was a significant inverse correlation between interferon-alpha and transforming growth factor-beta1 (r = - 0.743; p < 0.001), and HIV-RNA was present in inverse proportion to transforming growth factor beta1 (r = - 0.751; p < 0.001). In patients with severe AIDS-dementia, transforming growth factor-beta1 was undetectable, while interferon-alpha level were higher than in mild AIDS dementia and correlated positively to cerebral HIV-RNA. No significant difference was evident between these cytokines in the serum of ADC patients and in the control samples. Our study suggests that a relationship is possible between productive HIV infection in the cerebral nervous system and a heterogenous and different expression of the immune response via a complex interaction of cytokines with a differential modulation of the dementia phenotype.

AIDS Dementia Complex↗
PubMed1998

Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis: a correlation with clinical activity.

Levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-10 and transforming growth factor (TGF)-beta in cerebrospinal fluid (CSF) and serum of 29 patients with multiple sclerosis (MS) of the relapsing-remitting type and of 20 controls with other non inflammatory neurological diseases were studied. Sixteen patients were in the active phase of disease and 13 in remission. In CSF, higher IL-10 and TGF-beta concentrations were found in patients with a stable phase of MS, while in the active phase there were elevated levels of TNF-alpha and GM-CSF. These results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.

Adolescent↗
PubMed1997

Possible role of transforming growth factor-beta in relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) and serum levels of transforming growth factor (TGF)-beta and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in ten patients with definite multiple sclerosis (MS) of the relapsing-remitting type. CSF TGF-beta levels of MS patients in remission were significantly (p < 0.01) higher than of MS patients in active phase, and there was a significant inverse correlation (p < 0.05) between TGF-beta and slCAM-1 levels in the CSF of patients in both remitting and relapsing type. This is consistent with a possible down-regulation of TGF-beta on ICAM-1 expression and suggests a possible synthesis in the central nervous system of TGF-beta.

Adult↗
PubMed1996

Combined therapy with zidovudine, recombinant granulocyte colony stimulating factors and erythropoietin in asymptomatic HIV patients.

The aim of this randomized, comparative, double-blind study was to determine the efficacy of zidovudine (ZVD) either alone or in combination with recombinant granulocyte-colony stimulating factors (rG-CSF) and erythropoietin (Epo) in asymptomatic HIV-infected subjects with a CD4+ cell count < 500/mm3, classified as CDC II stage. We recruited 20 HIV Ab+ asymptomatic patients who were randomized into two groups: A and B. Group A was treated with ZVD at the dosage of 500 mg daily in combination with rG-CSF (10 micrograms/Kg/biweekly) and Epo (50 IU/Kg/biweekly). Group B was treated with ZVD (500 mg/day) alone. The primary end-point was progression to an AIDS-defining event and the secondary end-point included changes in the CD4+ cell count, p24 Ag status, beta-2-microglobulin, and ferritin levels. The patients of Group A showed no significant changes in transaminase, ferritin and beta-2-microglobulin levels while CD4 cells, Hb and neutrophil levels increased significantly compared to Group B (p < 0.001) and baseline values (p < 0.05). Conversely, 5 patients in Group B showed a significant decrease in CD4 cells (p < 0.01), Hb and neutrophil levels (p < 0.01) compared to baseline values, while beta-2-microglobulin increased (p < 0.05) compared to initial values. Our preliminary study may indicate that the combination of zidovudine with these hematopoietic growth factors could reduce the possibility of virus-related hematologic toxicity and could be more efficacious than zidovudine alone in prolonged therapy.

Adult↗
PubMed1993

Markers of activated T lymphocytes and T cell receptor gamma/delta+ in patients with multiple sclerosis.

We studied interferon-gamma (IFN-gamma), alpha-tumor necrosis factor (alpha-TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid and serum of 18 patients with multiple sclerosis (MS) and 10 subjects with other neurological diseases (OND). We also studied the cerebrospinal-fluid CD 69 expression, and T cells with T cell receptor (TcR) gamma/delta+. We found an increase of IFN-gamma (14.0 +/- 3.5 U/ml) and GM-CSF (8.0 +/- 3.4 pg/ml) levels in the cerebrospinal fluid of MS patients compared to the OND group (p < 0.005 and p < 0.01, respectively). The frequency of detectable cerebrospinal-fluid and serum alpha-TNF was similar in patients with MS and with OND. The cerebrospinal-fluid CD69 expression in lymphocytes was significantly higher in MS patients (15.0 +/- 9.9%) than in the control group (3.7 +/- 6.2%; p < 0.005). Comparable serum levels of IFN-gamma and GM-CSF were detected in patients with MS and in OND subjects. No significant difference in the incidence of TcR gamma/delta+ in the cerebrospinal fluid was found between the two groups. These results indicate an activation of T lymphocytes and macrophages in patients with MS. Our data do not suggest a role for an increased incidence of TcR gamma/delta+. However, we cannot rule out the possibility that these T cells could be present at the plaque site of MS patients.

Adult↗
PubMed1992

Cerebrospinal fluid cytokines in AIDS dementia complex.

We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1-alpha (IL-1-alpha), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV-seronegative subjects with other neurological diseases (OND). CSF TNF-alpha, IL-1-alpha and IL-6 were more frequently detectable in ADC patients than in OND subjects. These cytokines were also detectable in CSF of ADC patients with minimal symptoms. In contrast, the majority of both ADC and OND patients did not contain detectable serum levels of cytokines. Our data support the notion of intrathecal synthesis of cytokines in ADC patients and raise the possibility that activated macrophages may play a significant role in the pathogenesis of ADC.

AIDS Dementia Complex↗
PubMed1992

Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex.

Cerebrospinal fluid (CSF) and serum concentrations of beta-2-microglobulin (beta-2-m) were evaluated in 19 patients with clinically definite multiple sclerosis (MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other neurological diseases (OND). CSF beta-2-m and CSF/serum beta-2-m ratio were significantly higher in the patients with ADC than in the MS and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND patients. These findings indicate that CSF beta-2-m and CSF/serum ratio may be a useful marker in the diagnosis of ADC. In MS patients the beta-2-m CSF determinations are of no value.

AIDS Dementia Complex↗