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Biomedical subjects

M Bernardi

Publications and source records attributed to M Bernardi.

At least 73 records · Page 4Linked to original sources
PubMed2001

New infection with heterotypic hepatitis C virus in a patient with long-term hepatitis C virus eradication.

BACKGROUND: Experimental hepatitis C virus infection in chimpanzees has shown that natural hepatitis C virus infection does not induce protective immunity and reinfection can occur in seroconverted animals. AIM: To study the clinical, virological and histological outcome of a new infection sustained by a different hepatitis C virus strain after a primary infection with eradication of the original virus. PATIENTS AND METHODS: A young Italian man with chronic hepatitis C virus type 4 hepatitis was treated with Interferon therapy and achieved a sustained biochemical and virological response. After long follow-up, an asymptomatic flare-up of alanine transaminase occurred. This alanine transaminase increase was associated with serum hepatitis C virus RNA positivity and a low viral load, and the infecting hepatitis C virus genotype was type 3. The clinical and virological course of this new infection is described. RESULTS AND CONCLUSIONS: This report shows that there is no protective immunity against hepatitis C virus type 3 after infection by hepatitis C virus type 4 strain.

Adult↗
PubMed2001

Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis.

A 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m2 and increased each month by 10 mg/m2. It was then administered by continuous infusion until June 2000, starting at 20 mg/m2/d and tapering by 5 mg/m2 every 2 weeks to a final daily dose of 5 mg/m2/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis.

Aged↗
PubMed2001

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.

Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha-induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient.

The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and decoy cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few decoy cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.

BK Virus↗
PubMed2001

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status.

Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F(0)F(1)-ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta-F(1) subunit of the F(0)F(1)-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta-F(1) subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F(0)F(1)-ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.

ATP Synthetase Complexes↗
PubMed2001

Food deprivation exacerbates mitochondrial oxidative stress in rat liver exposed to ischemia-reperfusion injury.

Mitochondria undergo oxidative damage during reperfusion of ischemic liver. Although nutritional status affects ischemia-reperfusion injury in the liver, its effect on mitochondrial damage has not been evaluated. Thus, this study was designed to determine whether starvation influences the oxidative balance in mitochondria isolated from livers exposed to warm ischemia-reperfusion. Fed and 18- and 36-h food-deprived rats underwent partial hepatic ischemia followed by reperfusion. Mitochondria were isolated before and after ischemia and during reperfusion. Serum alanine transaminase was measured to assess liver injury. The mitochondrial concentrations of malondialdehyde, protein carbonyls and glutathione were determined as indicators of oxidative injury. Cell ultrastructure was assessed by transmission electron microscopy. Transaminase levels were greater in 18-h food-deprived than fed rats (after 120 min of reperfusion: 3872 +/- 400 vs. 1138 +/- 59 U/L, P < 0.01). Mitochondrial glutathione was lower in food-deprived than fed rats before and after ischemia, and during reperfusion. Food deprivation also was associated with significantly greater lipid and protein oxidative damage. Finally, more ultrastructural damage was observed during reperfusion in mitochondria from food-deprived rats. Prolonging the length of food deprivation to 36 h exacerbated significantly both the mitochondrial oxidative injury and the release of serum transaminases in rats (after 120 min of reperfusion: 5438 +/- 504 U/L, P < 0.01). Food deprivation was associated with greater mitochondrial oxidative injury in rat livers exposed to warm ischemia-reperfusion, and the extent of oxidative damage in mitochondria increased with the length of food deprivation.

Alanine Transaminase↗
PubMed2001

Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis.

BACKGROUND: The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM: To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS: Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS: Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high alpha fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline alpha fetoprotein levels > or =20 ng/ml. CONCLUSIONS: Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.

Antiviral Agents↗
PubMed2001

Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients.

OBJECTIVES: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. METHODS: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG performance status < or = 3, HIV-negative and no prior treatment. Thirteen patients (1996-1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. RESULTS: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. CONCLUSIONS: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.

Adult↗
PubMed2000

Effect of increasing dose of interferon on the evolution of hepatitis C virus 1b quasispecies.

The effects of interferon therapy on hepatitis C virus (HCV) genome are still controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non-structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were analyzed in HVR and NS5A by single-strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. However, at least one persistent strain was present in all patients. With low doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduction in the heterogeneity of the HVR quasispecies was observed after increase of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interferon sensitivity of some HCV strains may be dose dependent. The homogeneity of NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region.

5' Untranslated Regions↗
PubMed2000

Soluble CD30 serum level in HCV-positive chronic active hepatitis: A surrogate marker of disease activity?

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5; P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th(2)cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections.

Adult↗
PubMed2000

Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis.

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Adult↗
PubMed2000

Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study.

STUDY DESIGN: Construction of an international walking scale by a modified Delphi technique. OBJECTIVE: The purpose of the study was to develop a more precise walking scale for use in clinical trials of subjects with spinal cord injury (SCI) and to determine its validity and reliability. SETTING: Eight SCI centers in Australia, Brazil, Canada (2), Korea, Italy, the UK and the US. METHODS: Original items were constructed by experts at two SCI centers (Italy and the US) and blindly ranked in an hierarchical order (pilot data). These items were compared to the Functional Independence Measure (FIM) for concurrent validity. Subsequent independent blind rank ordering of items was completed at all eight centers (24 individuals and eight teams). Final consensus on rank ordering was reached during an international meeting (face validation). A videotape comprised of 40 clips of patients walking was forwarded to all eight centers and inter-rater reliability data collected. RESULTS: Kendall coefficient of concordance for the pilot data was significant (W=0. 843, P<0.001) indicating agreement among the experts in rank ordering of original items. FIM comparison (Spearman's rank correlation coefficient=0.765, P<0.001) showed a theoretical relationship, however a practical difference in what is measured by each scale. Kendall coefficient of concordance for the international blind hierarchical ranking showed significance (W=0.860, P<0.001) indicating agreement in rank ordering across all eight centers. Group consensus meeting resulted in a 19 item hierarchical rank ordered 'Walking Index for Spinal Cord Injury (WISCI)'. Inter-rater reliability scoring of the 40 video clips showed 100% agreement. CONCLUSIONS: This is the first time a walking scale for SCI of this complexity has been developed and judged by an international group of experts. The WISCI showed good validity and reliability, but needs to be assessed in clinical settings for responsiveness.

Australia↗
PubMed2000

Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet.

Although fatty liver (FL) is considered an innocuous condition, the frequent incidence of graft failure when FL are transplanted has renewed interest in the intracellular disorders causative of or consequent to fatty degeneration. Oxidative stress and nutritional status modulate the tolerance to reperfusion injury in control livers (CL), but very little is known in the case of FL. This study was designed to compare the oxidative balance in CL and FL from fed and food-deprived rats. Serum and liver samples were collected from fed and starved (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was assessed by transaminase activities and histology. The hepatic concentrations of glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than those with CL, whereas GSH and PC concentrations were not affected. Starvation impaired the oxidative balance in both groups. However, compared with the other groups, FL from food-deprived rats generally had the lowest hepatic concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein oxidation occurred in FL. These data indicate that fatty liver induced by consumption of a choline-deficient diet is associated with a lower level of antioxidants, which results in lipid peroxidation. Starvation further affects these alterations and extends the damage to proteins. In conclusion, steatosis and starvation may act synergistically on the depletion of antioxidants, predisposing fatty livers to a reduced tolerance to oxidative injury.

Animals↗
PubMed2000

Natural history of cirrhotic patients with small esophageal varices: a prospective study.

OBJECTIVE: Contrasting data are available on the natural history and bleeding risk of small esophageal varices. The aim of this prospective study was to evaluate a large series of consecutive cirrhotics with a first endoscopic diagnosis of small varices. METHODS: Between 1987 and 1992, 258 patients with small varices and no previous bleeding were enrolled. Patients were clinically examined every 6 months and were followed until a first episode of bleeding and/or death, or until June 1998. None received any treatment to prevent bleeding. Endoscopies were planned at 18-month intervals. RESULTS: The cumulative risk of bleeding was low (3% at 2 yr and 8% at 4 yr) and remained low in patients in whom varices remained small at 2nd endoscopy, whereas it increased significantly when varices enlarged. The increase of varices appeared to be rather linear in time: at the 2nd endoscopy varices remained small in 79% of patients and increased in 21%; at the 3rd endoscopy varices remained small in 55%, whereas at the 4th 33% of patients still had small varices. Clinical and biochemical data at the 1st and 2nd endoscopy were included in a multiple logistic regression analysis. Only the increase in Child-Pugh score appeared to be a significant predictor of enlarged varices; the risk of aggravation increased by 37.5% for every unit of impairment of the score. CONCLUSIONS: The present study shows that patients with small varices have a low bleeding risk. An increase in Child-Pugh score during follow-up suggests enlargement of varices, thus an increase in bleeding risk. In these patients closer endoscopic surveillance is recommended.

Chi-Square Distribution↗
PubMed1999

Prevalence and severity of dementia among northern Italian centenarians.

Using diagnostic criteria from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, dementia was clinically diagnosed in 57 (62%) of 92 centenarians living in two northern Italian provinces. The condition was severely disabling in approximately 70% of the demented patients. Although clinically diagnosed AD accounted for 79% of dementia cases, almost one third of patients with AD had risk factors for vascular dementia, suggesting that the aging brain may be susceptible to multiple additive factors that impair cognition.

Aged↗