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M Bernardi

Publications and source records attributed to M Bernardi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effects of the combined treatment with thalidomide, megestrol and interleukine-2 in cirrhotic patients with advanced hepatocellular carcinoma. A pilot study.

BACKGROUND: Thalidomide, an anti-angiogenic agent, does not have a good therapeutic effect for advanced hepatocellular carcinoma when used alone. Megestrol and interleukin-2 have been proposed as a palliative treatment for hepatocellular carcinoma. AIMS.: We assessed the effectiveness/safety of a combined therapy with thalidomide+megestrol+interleukin-2 in cirrhotic patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Nine cirrhotic patients with advanced hepatocellular carcinoma received oral megestrol (160 mg/day) and thalidomide (from 50 mg/day to the maximal tolerated dose). Four patients also received subcutaneous interleukin-2 (1 million U/day for 21 days/month). RESULTS: The maximal tolerated dose of thalidomide was 150 mg/day. All patients complained of sedation and other neurological or digestive adverse effects. In all but one patient the adverse effects disappeared after thalidomide withdrawal or dose reduction. Interleukin-2 administration caused a flu-like syndrome and a reaction at the injection site. During treatment, alpha-fetoprotein increased in six patients, remained stable in two and decreased in one. Eight patients showed tumour progression and one had a stable disease. Eight patients died. The median survival was 9.9 (range 2.6-18.6) months. CONCLUSION: In cirrhotic patients, the combined treatment with thalidomide+megestrol (+/-interleukin-2) does not control hepatocellular carcinoma growth, possibly due to the low tolerance to thalidomide and interleukin-2 preventing the use of appropriate dosages.

Aged↗
PubMed2005

Cultural recovery and determination of antimicrobial susceptibility in Helicobacter pylori by using commercial transport and isolation media.

BACKGROUND: Antimicrobial resistance of Helicobacter pylori is the main reason for eradication failure. We have studied the feasibility of a commercial transport medium for cultural recovery and subsequent drug susceptibility testing. PATIENTS AND METHODS: From March to December 2000, 79 consecutive gastric biopsies, positive in a rapid urease test, were transferred into a commercial transport medium and sent within 24 hours from the district hospital to the microbiological laboratory for culture and susceptibility testing. A commercial agar plate and an in-house Wilkins-Chalgren agar plate were used for culture. Susceptibility data were compared with data collected from 1992 to 2003 in the University Hospital of Zurich. RESULTS: Cultural recovery and susceptibility testing of H. pylori was successful in 55 of 79 patients. In 17 cases cultural recovery failed because of technical problems (n = 14), long transport time (n = 1) and unknown reason (n = 2). Failure of susceptibility testing (n = 7) was mainly due to fungal overgrowth. Resistance to metronidazole and clarithromycin was found in 15 (27%) and in 12 patients (22%), respectively; resistance to amoxicillin was not observed. Five patients (9%) showed resistance both to metronidazole and to clarithromycin. Eradication therapy failed in all patients with macrolide resistance. Resistance rates were higher in females than in males; 30% vs 12% for clarithromycin and 33% vs 20% for metronidazole. Resistance to metronidazole was significantly lower in Swiss patients (15%) than in non-Swiss patients (39%). CONCLUSION: Antimicrobial resistance data can reliably be obtained by sending the biopsy specimen in a commercial transport medium to a microbiological laboratory. This is especially important after eradication failure. Resistance to metronidazole and clarithromycin is highly prevalent and more common in women and non-Swiss patients.

Amoxicillin↗
PubMed2005

Focal nodular hyperplasia after busulfan treatment.

The case of a 48-year-old woman in whom focal nodular hyperplasia of the liver developed after busulfan therapy was administered for essential thrombocytosis is described. Focal nodular hyperplasia is a reactive disorder related to a circulation disorder. The close temporal relation between the haematological disease, busulfan treatment and the appearance of hyperplastic diseases of the liver in our patient supports the possibility that the association of the events might not be casual.

Busulfan↗
PubMed2005

Oxidative injury in rat fatty liver exposed to ischemia-reperfusion is modulated by nutritional status.

BACKGROUND AND AIMS: Oxidative stress contributes to ischemia-reperfusion injury in fatty livers. This study aimed to determine whether glycogen depletion influences this oxidative injury and whether the administration of glucose can be protective. METHODS: Rats with choline deficiency-induced fatty liver underwent hepatic ischemia-reperfusion. Experimental groups: (1) fed rats; (2) 18 h fasted rats; (3) 18 h fasted rats supplemented with glucose prior to surgery. The thiobarbituric acid-reactive substances, protein carbonyls and total glutathione concentrations were measured in liver tissue and isolated mitochondria as parameters of oxidative stress before and after ischemia and during reperfusion. The mitochondrial F1-ATPase content and the serum alanine transaminase were also determined. RESULTS: With respect to fed rats, fasted rats exhibited an increased oxidative injury in both liver tissue and isolated mitochondria throughout the experiment with the only exception of thiobarbituric acid-reactive substances, which were not affected by the nutritional status in liver tissue. Fasted rats showed a significantly lower F1-ATPase content and higher alanine transaminase levels. Glucose supplementation significantly reduced the fasting-associated exacerbation of oxidative stress and liver injury and the F1-ATPase exhaustion. CONCLUSIONS: These data indicate that the pre-existing hepatic glycogen content modulates the oxidative damage in rat fatty livers exposed to ischemia-reperfusion injury and that the energetic substrate supplementation may represent a clinically feasible protective strategy.

Alanine Transaminase↗
PubMed2005

Transthoracic electrical bioimpedance: a non-invasive technique for the evaluation of the haemodynamic alterations in patients with liver cirrhosis.

BACKGROUND/AIM: Transthoracic electrical bioimpedance is a non-invasive technique for the evaluation of systemic haemodynamics. Compared to Doppler ultrasound, it has the advantage of being operator-independent, providing continuous monitoring and being less influenced by postural changes. Until now, transthoracic electrical bioimpedance has been applied to a very limited extent in liver cirrhosis. We, therefore, aimed to compare transthoracic electrical bioimpedance and echocardiography in the assessment of haemodynamic status in cirrhotic patients. PATIENTS/METHODS: Thirteen patients with compensated cirrhosis, 10 patients with cirrhosis and ascites and 12 controls were enrolled. Haemodynamic parameters (stroke volume, cardiac output, heart rate, mean arterial pressure and vascular peripheral resistance) were assessed simultaneously by transthoracic electrical bioimpedance monitoring with BioZ.com for at least 10 min and Doppler ultrasound. RESULTS: The absolute mean values of haemodynamic parameters obtained by the two techniques were quite similar in all groups; furthermore, a good agreement between transthoracic electrical bioimpedance and echocardiography measurements was found for all the parameters. Finally, transthoracic electrical bioimpedance proved easy to employ and provided continuous real-time monitoring of cardio-circulatory variations. CONCLUSIONS: The present study showed a significant correlation between transthoracic electrical bioimpedance and echocardiography in the assessment of systemic haemodynamics in patients with cirrhosis, supporting the employment of transthoracic electrical bioimpedance in pathophysiological studies requiring real-time continuous monitoring of haemodynamic parameters.

Adult↗
PubMed2005

Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma.

An interaction between the protein kinase (PKR)-eIF2-alpha phosphorylation homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell protein kinase (PKR) may affect the control of protein synthesis and cell growth. In an attempt to investigate the genetic variability of the E2-PePHD domain in hepatocellular carcinoma (HCC), we studied sera and liver tissues from HCC patients. The partial E2-PePHD region was analysed by direct sequencing of the sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis (CAH), and tumoral and non-tumoral liver tissues from 13 HCC patients. A similar number of mutations was detected within the E2 domain in the HCC and CAH cases, but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660, eight of which involved a change in the same aa (alanine instead of serine; A/S). No such mutation was detected in any of the PePHD sequences from the CAH patients: this difference was statistically significant (P = 0.008). The aa change at position 660 was also found in two sequences from tumoral but not non-tumoral tissue from the same liver. The analysis of 461 sequences obtained from GenBank supports the conclusion that the observed aa change is an infrequent event in HCV-infected patients, thus suggesting that it could be associated with HCC.

Aged↗
PubMed2005

Cytokine profile of peripheral blood mononuclear cells from patients with different outcomes of hepatitis C virus infection.

SUMMARY: The relationship between the balance of helper T-cell type 1 (Th1) or type 2 (Th2) cytokines and the clinical course of hepatitis C virus (HCV) infection is unclear. We evaluated Th1 [interleukin (IL)-2, interferon-gamma (IFN-gamma)] and Th2 cytokine (IL-4, IL-10) and 2,5-oligoadenylate synthetase (OAS, an IFN-induced antiviral protein) production by peripheral blood mononuclear cells from 10 healthy anti-HCV-positive individuals (group A), 10 HCV-RNA-positive with persistently normal alanine aminotransferase (ALT) levels (group B), 10 HCV-RNA-positive with abnormal ALT (group C) and 10 uninfected healthy controls. IL-2 production was significantly increased in group B when compared with all the other groups. No difference was found for IFN-gamma. IL-4 was significantly higher in group C than in both group B (P = 0.0006) and controls (P = 0.004). Compared with controls, IL-10 was significantly decreased in group A (P = 0.013) and B (P = 0.004). The production of 2,5-OAS was significantly higher in group B than in A (P = 0.04) and in C (P = 0.004). Finally, in all HCV-RNA-positive patients, a significant correlation was found between ALT and both IL-2 (r = -0.78; P = 0.0008) and IL-4 (r = 0.75; P = 0.0008). IN CONCLUSION: (i) subjects who cleared HCV showed a cytokine profile similar to controls; (ii) a preferential shift towards a Th1 profile seems associated with a more favourable clinical outcome in chronic hepatitis C; and (iii) a prevalent Th2 profile seems implicated in HCV pathogenesis and severity of liver disease.

Adult↗
PubMed2005

Human herpesvirus-8-related Kaposi's sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin.

The iatrogenic form of Kaposi's sarcoma (KS) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus-8) is still controversial. Available experiences on the effect of the anti-herpes viruses drug cidofovir provide conflicting results. Herein, we report the clinical, histological, and virological features of a liver transplant recipient successfully treated with a combined therapy of cidofovir and liposomal daunorubicin, associated with a reduction of the immunosuppressive regimen, for an advanced cutaneous and visceral KS.

Antibiotics, Antineoplastic↗
PubMed2005

Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.

Antibiotic Prophylaxis↗
PubMed2004

Genetic variability of hepatitis C virus in HBV/HCV co-infection and HCV single-infection.

To describe the virological profile of HCV in HBV/HCV co-infection, we investigated the variability of HVR-1 and NS5A domains, which may be involved in viral persistence and replication efficiency. We studied 95 patients: 37 with serological markers of HBV/HCV co-infection, 33 with single HBV and 25 with single HCV infection. HVR-1 complexity and NS5A gene variability were respectively explored by means of PCR-SSCP and direct sequencing. Serum HBV genomes were detected in all coinfected patients: 19 also had circulating HCV particles (group BC-I), whereas HCV were undetectable in the other 18 (group BC-II). Group BC-I was characterised by a significantly lower HBV replication capacity, that reflects the replicative dominance of HCV, although the dominant virus had the same degree of variability as the HCV in single infection. HBV viral load was higher in group BC-II, but not significantly different from that observed in the single infection. Our data indicate an alternation in replicative dominance in co-infection: HBV can suppress HCV replication to undetectable levels, whereas HCV may reduce but does not abrogate the replication capacity of HBV. Furthermore, in the cases of HCV dominance, circulating HBV genomes did not have a significant effect on the viral heterogeneity of HCV.

Adult↗
PubMed2004

The rational use of albumin in patients with cirrhosis and ascites. A Delphi study for the attainment of a consensus on prescribing standards.

BACKGROUND: Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital. AIMS: Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. METHODS: The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. RESULTS: The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. CONCLUSIONS: For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

Albumins↗
PubMed2004

Determinants of sit-to-stand capability in the motor impaired elderly.

Among the healthy elderly, sit-to-stand (STS) movement largely depends on: (a) trunk bending momentum, (b) centre of gravity (CG) position before the body rises and (c) lower limb extensor muscle strength. Because determining whether (c) improvement would affect STS capability in the motor impaired elderly (MIE) has been recommended, we studied the relative importance of (a), (b) and (c) in determining a successful fast STS movement comparing the healthy elderly with MIE with orthopaedic disorders studied before and after a rehabilitation program. Force platform was used to measure body's posture and kinematics during a STS test and therefore to assess (a), (b) and maximum vertical velocity (VVpeak), assumed as outcome measurement. Knee extensor maximal isometric voluntary contraction normalized by body mass (nMVC) was an indicator of (c). A multiple regression model was built to predict VVpeak from the three determinants of STS movement. In both groups, the model significantly determined VVpeak, with (a) and (c) being significant predictors of VVpeak and (a) being the major predictor. Rehabilitation was effective in improving nMVC. This process resulted in a change of the relative importance of (a) and (c), strength becoming the major predictor of VVpeak. In conclusion the present study demonstrates that a rehabilitative intervention aimed at increasing strength is effective in improving STS capability in MIE.

Aged↗
PubMed2004

Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.

In this pilot study, we evaluated the efficacy of interferon-alpha (IFN) plus Thymosin-alpha 1 (TA1) to that of IFN alone in naive patients with chronic hepatitis C. Twenty-two patients were randomized to receive interferon-alpha 2b (3 million units three times a week) plus thymosin-alpha l (900 microg/m2 body surface area) and 19 received interferon-alpha 2b alone at the same dose. Patients were treated for 6 months and followed up for another 6 months. Biochemical (alanine aminotransferase values) and virological (hepatitis C virus-RNA) responses to treatment were determined. Combination treatment showed significantly higher efficacy than monotherapy in achieving virological end-of-treatment response (P = 0.03). At 6-month follow up, the sustained biochemical and virological response was not different between the two groups. Our results indicate that the immune modulator TA1 may enhance the end-of-treatment response in naive patients with chronic hepatitis C. Higher doses and/ore more prolonged courses as well as the association with new interferon formulation such as pegylated interferons could improve the sustained response rates to this treatment.

Adjuvants, Immunologic↗
PubMed2004

High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance.

The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow-up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long-term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3-84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research.

Adult↗
PubMed2004

[A minimum medical GIS database (MMDb) for Europe].

Geographic information systems (GIS) and remote sensing (RS) technologies are being used increasingly to study the spatial and temporal patterns of some parasitic diseases of medical and veterinary importance. At the same time, the incorporation of GIS in this field shows the scarcity of the data and images available, which sometime discourage researchers that still look at GIS as a system too difficult and unusable for medical study. Aware of this problem and supported by success of earlier MMDb's for Africa, Asia and South America, the authors' aim is to construct and offer an MMDb for Europe. The initial MMDb is composed with vector images covering an area situated from -11 degrees-70 degrees N to 58 degrees-30 degrees E. Specifically, data layers include: a) Global Moderate-Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) 16 days at 250 m spatial resolution designed to provide consistent spatial and temporal comparisons of vegetation conditions, supplied in the MMDb as seasonal and annual composite images from 2000 to 2003, b) MODIS Land Surface Temperature (LST) calculated from daytime and nighttime observations at 8 day intervals at 1 km spatial resolution, supplied in the MMDb as seasonal and annual composites images for day (maximum) temperatures, night (minimum) temperatures from 2000 to 2003, c) GTOPO30 Digital Elevation Model (DEM) at 1 km spatial resolution, d) United States Geological Survey (USGS) Land use/land cover scheme, e) USGS actual and potential evapotranspiration supplied for all 12 months as a grid at 50 km spatial resolution, f) USGS precipitation showing the amount of rainfall for all 12 months supplied as a grid at 50 km spatial resolution, g) USGS shapefiles of administrative and political boundaries, cities, towns, villages, lakes, rivers, streams, road, railroads and more. The MMDb projection will be in geographic latitude-longitude, decimal degree format. This global format is most commonly used for public access map database resources and can be readily re-projected as needed for compatibility with various national mapping systems. There is no "required" software, and end users need only common commercial GIS software packages that have mutual import-export functions. Additionally, the MMDb is meant to be a dynamic resource that end users may improve and modify with other regional data.

Animals↗
PubMed2003

Gamma-hydroxybutyric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study.

Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses.

Alcohol Drinking↗