Prophylaxis and treatment of hepatis B virus infection after liver transplantation.
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Antiviral Agents↗
Biomedical subjects
M Bernardi
Publications and source records attributed to M Bernardi.
Amplitude and spectral characteristics of biceps Brachii sEMG depend upon speed of isometric force generation.
In the present study the influence of speed of contraction on the interplay between recruitment and firing rate of motor units (MUs) was assessed. The surface electromyographic (sEMG) signal was recorded in nine healthy subjects from the right biceps brachii using a linear electrode array during ramp isometric contractions (from 0 to 100% of the maximal voluntary force, MVC) at 5, 10, and 20% MVC s(-1) (ramp phase), followed by 10 s of sustained MVC (hold phase). The median frequency (MDF), Root Mean Square (RMS) and conduction velocity (CV) of sEMG, were computed on adjacent epochs covering a force range of 5% MVC each. Full motor unit recruitment (FMUR) point was assessed as the force level at which MDF reached its maximum value; the MDF decay during the hold phase was taken as an index of localized muscle fatigue. At 5% MVC s(-1), FMUR was reached at 52.3% MVC. At 10%MVC s(-1) FMUR was achieved at 58% MVC; while at 20% MVC s(-1) FMUR point was located at 77% MVC, being statistically different from 5 and 10% MVCs(-1) ramps (p<0.05). The MDF decay was steeper at higher speed. CV modifications mirrored those reported for MDF. The RMS increased in a curvilinear fashion and the maximum value was always attained during the hold phase. Our findings suggest that MU recruitment strategies are significantly related to the speed of contraction even in a single muscle.
Adult↗
Adaptation of subcellular glutathione detoxification system to stress conditions in choline-deficient diet induced rat fatty liver.
The response of fatty liver to stress conditions (t-butyl hydroperoxide [t-BH] or 36 h of fasting) was investigated by assessing intracellular glutathione (GSH) compartmentation and redox status, GSH peroxidase (GSH-Px) and reductase (GSSG-Rx) activities, lipid peroxidation (TBARs) and serum ALT levels in rats on a choline-deficient diet. Baseline cytosolic GSH was similar between fatty and normal livers, while the mitochondrial GSH content was significantly lower in fatty livers. With the except of cytosolic GSH-Px activity, steatosis was associated with significantly higher GSH-related enzymes activities. Liver TBARs and serum ALT levels were also higher. Administration of t-BH significantly decreased the concentration of cytosolic GSH, increased GSSG levels in all the compartments, and increased TBARs levels in cytosol and mitochondria and serum ALT; all these alterations were more marked in rats with fatty liver. Fasting decreased the concentration of GSH in all the compartments both in normal and fatty livers, increased GSSG, TBARs and ALT levels, and decreased by 50% the activities of GSH-related enzymes. Administration of diethylmaleimide (DEM) resulted in cytosolic and microsomal GSH pool depletion. Administration of t-BH to DEM-treated rats further affected cytosolic GSH and enhanced ALT levels, whereas the application of fasting to GSH depleted rats mainly altered the mitochondrial GSH system, especially in fatty livers. This study shows that fatty livers have a weak compensation of hepatic GSH regulation, which fails under stress conditions, thus increasing the fatty liver's susceptibility to oxidative damage. Differences emerge among subcellular compartments which point to differential adaptation of these organelles to fatty degeneration.
Alanine Transaminase↗
Interferon-alpha combined with ketoprofen as treatment of naïve patients with chronic hepatitis C: a randomized controlled trial.
In this randomized controlled study, we evaluated the efficacy and safety of interferon-alpha combined with ketoprofen to that of interferon-alpha alone in naïve patients with chronic hepatitis C. Forty patients were randomized to receive Interferon-alpha2a (3 million units three times a week) and ketoprofen (150 mg twice a day) and 40 to receive only interferon-alpha2a at the same dose. Patients were treated for 6 months and followed up for 6 months. Response was defined by undetectable HCV-RNA in serum at the end-of-treatment and after 6 months from the completion of therapy (long term response). At the end of treatment the response was similar in the two group. However, combination treatment showed significantly higher efficacy than monotherapy in achieving long term response (10%vs 32.5%; P = 0.014). Overall adverse events were similar in the two groups. 'Flu-like syndrome was significantly less common in the ketoprofen plus interferon group which experienced a significantly higher incidence of epigastric pain'. Our results indicate that the combination of ketoprofen plus interferon is significantly more effective than interferon alone in the treatment of naïve patients with chronic hepatitis C and is well tolerated. However this combined treatment appears to be less effective than the association of pegylated IFN and ribavirin which represent the current standard treatment. Thus, the role of ketoprofen in the treatment of chronic hepatitis C needs to be further evaluated against such a treatment.
Adult↗
[Are autopsies still useful?].
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Autopsy↗
Evidence of oxidative imbalance in long-term liver transplant patients.
BACKGROUND: Oxidative stress in patients undergoing liver transplantation results both from the pre-existing cirrhosis and ischaemia-reperfusion injury related to surgery. Previous studies have provided information limited to the immediate post-operative period. It remains to be established whether this oxidative imbalance is reversed in a longer time. AIM, METHODS AND PATIENTS: This study aimed to compare plasma concentrations of thiobarbituric acid-reactant substances and alpha-tocopherol in 20 cirrhotic patients before liver transplantation and 22 patients in whom transplant had been carried out at least 6 months previously. Thirty healthy age and sex-matched volunteers served as controls (cross-sectional study). Five patients were evaluated before and after liver transplantation (longitudinal study). RESULTS AND CONCLUSIONS: Pre-transplant patients showed greater thiobarbituric acid-reactant substances and lower alpha-tocopherol levels than controls. Transplanted patients presented lower thiobarbituric acid-reactant substances and greater alpha-tocopherol levels than cirrhotic patients without reaching, however, the levels observed in controls. No correlations were found between oxidative parameters and liver tests. Hypertransaminasaemia, liver disease recurrence, and rejection episodes did not significantly influence the oxidative parameters. In the longitudinal study, transplantation induced a significant decrease in plasma thiobarbituric acid-reactant substances and a rise in alpha-tocopherol. Although a long-term improvement in the oxidative injury observed in cirrhotic patients occurs after liver transplantation, mild oxidative stress persists even in successfully transplanted patients.
Adult↗
Fibrovascular polyp of the esophagus.
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Aged↗
Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome.
BACKGROUND: Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. METHODS: Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. RESULTS: Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). COMMENT: Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.
Adult↗
Increased generation of reactive oxygen species in isolated rat fatty liver during postischemic reoxygenation.
BACKGROUND: Whether fatty infiltration of the liver influences the generation of reactive oxygen species (ROS) during reperfusion is unclear. Thus, this study aimed to compare the ROS formation that occurs during postanoxic reoxygenation in isolated normal and fatty livers. METHODS: Isolated livers from fed Sprague-Dawley rats with normal or fatty livers induced by a choline-deficient diet were reperfused at 37 degrees C for 60 min with an oxygenated medium containing 10 microM of lucigenin after 1 hr of warm ischemia. Superoxide anion generation was assessed by the chemiluminescence (CLS) signal emitted from the organ surface. The hepatic content of malondialdehyde (MDA) and glutathione was determined at the end of reperfusion. Tissue injury was evaluated by the liver histology and the alanine aminotransferase (ALT) release in the perfusate. RESULTS: CLS started rapidly with reoxygenation and it diffused to the whole organ in both groups. However, CLS emission was significantly higher in fatty liver (after 10 min: 812.425+/-39.898 vs. 294.525+/-21.068 photons/cm2/sec; P<0.01). A greater concentration of MDA was measured at the end of reoxygenation in fatty liver. Finally, the liver histology and the ALT release indicated a greater injury in steatotic than normal liver. CONCLUSIONS: The CLS technique allows a direct visualization and comparison of ROS generation from the organ surface. Fatty infiltration increases ROS generation in the liver during postischemic reoxygenation, likely leading to the greater lipid peroxidation observed in these experiments. The increased oxidative stress may contribute to the reduced tolerance of steatotic livers to ischemia-reperfusion injury.
Alanine Transaminase↗
A global network for the control of snail-borne disease using satellite surveillance and geographic information systems.
At a team residency sponsored by the Rockefeller Foundation in Bellagio, Italy, 10-14 April 2000 an organizational plan was conceived to create a global network of collaborating health workers and earth scientists dedicated to the development of computer-based models that can be used for improved control programs for schistosomiasis and other snail-borne diseases of medical and veterinary importance. The models will be assembled using GIS methods, global climate model data, sensor data from earth observing satellites, disease prevalence data, the distribution and abundance of snail hosts, and digital maps of key environmental factors that affect development and propagation of snail-borne disease agents. A work plan was developed for research collaboration and data sharing, recruitment of new contributing researchers, and means of access of other medical scientists and national control program managers to GIS models that may be used for more effective control of snail-borne disease. Agreement was reached on the use of compatible GIS formats, software, methods and data resources, including the definition of a 'minimum medical database' to enable seamless incorporation of results from each regional GIS project into a global model. The collaboration plan calls for linking a 'central resource group' at the World Health Organization, the Food and Agriculture Organization, Louisiana State University and the Danish Bilharziasis Laboratory with regional GIS networks to be initiated in Eastern Africa, Southern Africa, West Africa, Latin America and Southern Asia. An Internet site, www.gnosisGIS.org, (GIS Network On Snail-borne Infections with special reference to Schistosomiasis), has been initiated to allow interaction of team members as a 'virtual research group'. When completed, the site will point users to a toolbox of common resources resident on computers at member organizations, provide assistance on routine use of GIS health maps in selected national disease control programs and provide a forum for development of GIS models to predict the health impacts of water development projects and climate variation.
Animals↗
Linkages between FAO agroclimatic data resources and the development of GIS models for control of vector-borne diseases.
The Food and Agriculture Organization (FAO) of the United Nations is the largest specialized UN Agency dealing with agriculture, forestry and fishery, particularly in the developing countries. One of its technical services, placed under the Sustainable Development Department, has the responsibility to provide information on environment and natural resources as related to food and agriculture. It includes, among others, expertise in remote sensing, geographic information systems and agrometeorology, production of global environmental digital datasets, meteorological and remote sensing data collection and analysis at near real-time, development of methodologies, models and tools for data standardization, collection, spatialization, analysis and dissemination, networking and information sharing, development of integrated information management systems. Some experience has also been gained in the use of climatic digital datasets for spatial modeling of crop pests and diseases. The description of mapping the distribution of the Western Corn rootworm (Diabrotica virgifera) in Europe as a function of environmental conditions is presented as well as the global assessment of environmental potential constraints based on processing of digital datasets. A simple spatial interpolation routine is briefly explained.
Animals↗
MET receptor is overexpressed but not mutated in oral squamous cell carcinomas.
Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF-induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive-metastatic behavior.
Adult↗
Intranasal mupirocin reduces sternal wound infection after open heart surgery in diabetics and nondiabetics.
BACKGROUND: This study was designed to determine whether decreasing nasal bacterial colonization by applying Mupirocin (MPN) intranasally decreases sternal wound infections. METHODS: We prospectively followed 992 consecutive open heart surgery (OHS) patients who did not receive MPN prophylaxis (group I) from January 1, 1995 to October 31, 1996. Group II consisted of 854 consecutive patients followed prospectively from December 1, 1997 to March 31, 1999 treated with intranasal MPN given on the evening before, the morning of OHS, and twice daily for 5 days postoperatively. RESULTS: There was a significant difference in the rate of overall sternal wound infections between the untreated (group I) and the treated group (group II): 2.7% (27 of 992) versus 0.9% (8 of 854) (p = 0.005). The difference was also significant in the diabetic subgroup: 5.1% (14 of 277) (group I) versus 1.9% (5 of 266) (group II) (p = 0.04) and the nondiabetic group: 1.8% (13 of 715) (group I) versus 0.5% (3 of 588) (group II) (p = 0.03). The cost of MPN treatment was $12.47 per patient compared with $81,018 +/- $41,567 for a deep wound infection with no antibiotic-related complications recorded. CONCLUSIONS: Prophylactic intranasal MPN is safe, inexpensive, and very effective in reducing the overall sternal wound infections by 66.6%.
Administration, Intranasal↗
Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.
BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. METHODS: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. RESULTS: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019). CONCLUSION: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.
Adult↗
Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.
BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.
Aged↗
Transjugular intrahepatic splenosystemic shunt in a patient with portal vein thrombosis.
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Female↗
Exercise induced muscle damage and recovery assessed by means of linear and non-linear sEMG analysis and ultrasonography.
This study was aimed at investigating the time-course and recovery from eccentric (EC) exercise induced muscle damage by means of surface electromyography (sEMG), ultrasonography (US), and blood enzymes. Five subjects (EC Group) performed two bouts of 35 EC maximum contractions with the biceps brachii of their non dominant arm, five subjects were tested without performing EC (Control Group: CNT). The maximal isometric force (MVC) was measured. Force and sEMG signals were recorded during 80% MVC isometric contractions. In EC and CNT subjects US assessment on non-dominant biceps brachii was performed; creatin kinase (CK) and lactic dehydrogenasis (LDH) plasma levels were also assessed. Force, sEMG and CK-LDH measurements were performed before EC and after it periodically for 4 weeks. The sEMG was analysed in time and frequency domains; a non-linear analysis (Lyapunov 1st exponent, L1) of sEMG was also performed. After EC, the MVC was reduced by 40% on average with respect to the pre-EC values. A significant decrease in the initial frequency content, and in the MDF and L1 decay (13-42% less than the pre-EC values, respectively) was also observed. The sEMG amplitude (Root Mean Square, RMS) was unchanged after EC. The US revealed an increase in muscle belly thickness and in local muscle blood flow after EC. A complete recovery of all the considered parameters was achieved in two weeks. In conclusion sEMG analysis was confirmed as an early indicator of muscle damage. Muscle recovery from damage is followed by both sEMG and US and this may have useful clinical implications. Non linear analysis (L1) was revealed to be sensitive to early sEMG modifications induced by EC as well as able to follow the post EC changes in the sEMG.
Adult↗
Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study.
BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option.
Aged↗