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Background. Minimal hepatic encephalopathy (MHE) represents a common complication present in well-compensated cirrhotic patients that impairs patients' daily functioning and health-related quality of life (HRQL). Acetyl- l-carnitine (ALC) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE. Objective. This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE. Study design. This was a randomized, double-blind, placebo-controlled study. Sixty-seven patients with MHE were recruited to the study. They were randomly assigned to two groups and received either 2 g acetyl- l-carnitine twice a day ( n == 33) or placebo ( n == 34) for 90 days. The primary efficacy measures were changes in aspartate aminotransferase, alanine aminotransferase, γγ-glutamyl-transpeptidase, albumin, alkaline phosphatase, prothrombin time, and ammonia. Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. Results. At the end of the study period, between the two groups, we observed a significant difference in physical function ( p < 0.001), role physical ( p < 0.001), general health ( p < 0.001), social function ( p < 0.05), role emotional ( p < 0.05), mental health ( p < 0.05), Beck Depression Inventory ( p < 0.001), TMT-B s ( p < 0.001), State Trait Inventory ( p < 0.001), urea ( p < 0.05), NH4 ++ ( p < 0.001), and bilirubin ( p < 0.001). Conclusions. This study shows that ALC treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitine's supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), γ-glutamyl-transpeptidase (γ-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-α (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic-related disorder characterized by fatty infiltration of the liver in the absence of alcohol consumption. NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which might progress to end-stage liver disease. This progression is related to the insulin resistance, which is strongly linked to the metabolic syndrome consisting of central obesity, diabetes mellitus, and hypertension. Earlier, the increased concentration of intracellular fatty acids within hepatocytes leads to steatosis. Subsequently, multifactorial complex interactions between nutritional factors, lifestyle, and genetic determinants promote necrosis, inflammation, fibrosis, and hepatocellular damage. Up to now, many studies have revealed the mechanism associated with insulin resistance, whereas the mechanisms related to the molecular components have been incompletely characterized. This review aims to assess the potential molecular mediators initiating and supporting the progression of NASH to establish precocious diagnosis and to plan more specific treatment for this disease. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-L: -carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90 days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90 days in group A treated with ALC, we observed a significant decrease in prothrombin time (P < 0.001), bilirubin serum levels (P < 0.01), AST (P < 0.001), fasting NH(4) serum levels (P < 0.001), Trail Making Test-A (P < 0.001) and Trail Making Test-B (P < 0.001), and a significant increase in albumin serum levels (P < 0.005), MMSE test (P < 0.001), Symbol Digit Modalities Test (P < 0.001), BDT (P < 0.001), AVL long-term test (P < 0.001) and AVL total test (P < 0.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are few studies about the relationship between HCV and the development of other tumors. We consider the prevalence of HCV infection in elderly cancer patients who have tumors different from that in hepatocellular carcinoma and non-Hodgkin''s lymphoma. Methods: We evaluated the prevalence of HCV infection in 236 elderly cancer patients in comparison with 300 elderly volunteers. Cancer patients presented a variety of tumors other than hepatocarcinoma and lymphoma, namely, colorectal (n =66), breast (n =44), bladder (n =40), prostate (n =30), lung (n =22), kidney (n =15), pancreatic (n =6), thyroid (n =5), cervical (n =4), melanoma (n =3) and vaginal (n =1). Results: Among the 236 elderly cancer patients, 87 were positive for HCV antibodies (36%) and, among the 300 elderly patients, 32 were positive (10%). A comparison between the two groups revealed a statistically significant difference (p <0.001) between patients with kidney cancer, bladder cancer or prostate cancer, and the control group. Conclusions: The high anti-HCV prevalence in elderly cancer patients may be due to several mechanisms. These patients are more prone to acquire an HCV infection because of their frequent hospitalizations and the immunological changes in patients with tumors may lower their threshold for HCV infection. [Copyright &y& Elsevier]

Several letters to the editor are presented presenting several the medical cases including the role of carnitine in reducing physical and mental fatigue, the case of vitamin D deficiency in primary aldosteronism, and the diagnosis of intestinal ascariasis.

Background: Interferon (IFN)-α-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNα-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNα-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone. Patients and methods: We evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNα-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNα-2b (Intron® A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400mg twice daily (morning and night) [for patients weighing <75kg] or 500mg twice daily (for those weighing ≥75kg). The planned treatment period was 6 months. Results: Both IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered. Conclusion: The combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection. [ABSTRACT FROM AUTHOR]

Although serological findings indicate the presence of a relationship between Helicobacter pylori (HP) and vascular disease, no data have been reported about a possible association of HP with dementia. The aim of the present study was to determine whether chronic HP infection might play a role in Alzheimer''s disease (AD).Plasma homocysteine level, serum folate and vitamin B12 concentrations, plasma pyridoxal phosphate level, IgG and IgA antibodies to HP, and C-reactive protein (CRP) were determined in 30 AD patients, 30 patients affected by vascular dementia (VaD), and 30 control subjects. All patients and control subjects were matched for age, educational level, and nutritional and socioeconomic status. None of the subjects had a history of chronic gastritis, peptic ulcer, gastric cancer, or major abdominal surgery.HP-IgG level was significantly increased in VaD patients as compared to controls and AD patients, while AD patients had HP-IgG levels higher than those of normal controls. HP-IgA levels were equally increased in both VaD and AD patients. CRP was higher in AD patients than in VaD patients and controls, although CRP levels in VaD patients were also significantly increased.The present study found an association between HP infection and AD. The question remains as to whether this association is due to the ubiquity of HP, or whether it contributes to the neuroinflammatory process in AD. The relationship between HP and AD, if confirmed by additional studies with a greater number of patients, may have important clinical and therapeutic implications. [Copyright &y& Elsevier]

The association between elevated plasma levels of homocysteine (Hcy) and nutritional status has been shown in Alzheimer disease (AD) patients and also in vascular dementia (VaD). Moreover, a previous study provided evidence that the relation between a high Hcy level and low vitamin B12 and folate levels in AD patients is due to biochemical damage, rather than a nutritional deficit. The purpose of this study was to investigate the relationship between plasma Hcy levels and vitamins involved in its metabolism in AD and VaD. Twenty-two VaD patients, 22 AD patients and 24 healthy subjects were studied for Hcy, vitamin B12, vitamin B6 and folate. All patients and control subjects were comparable for age, educational level, nutritional and socioeconomic status. None of them showed macrocytic anemia or impaired renal function. Hcy was significantly increased in VaD patients (26.0±6.58 μmol/l) as compared to controls (10.7±3.0 μmol/l) and AD patients (22.3±4.51 μmol/l; p<0.001); however, AD patients also showed increased levels of Hcy. Folates were significantly reduced in both VaD (10.8±2.81 nmol/l) and AD (10.0±2.72 nmol/l; p<0.001) patients, while vitamin B12 showed significantly reduced levels only in AD patients (392.1±65.32 pmol/l; p=0.02). Vitamin B6 was not significantly different in the three groups. Increased levels of Hcy associated with low vitamin B12 plasma levels were found only in AD patients. This observation led us to consider that vitamin B12 metabolism does not represent the direct consequence of the nutritional status and suggests that neuronal damage results in a functional vitamin B12 deficiency, as emphasized by recent reports. New therapeutic strategies are necessary, considering that available pharmaceutical forms of vitamin B12 are not utilized by neurons in oxidative stress conditions. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is a sulfur-containing metabolite of methionine and is an emerging independent risk factor for atherosclerosis. Previous studies have shown that age, gender, renal function and folic acid intake are the main factors influencing total plasma Hcy levels in humans. A unique approach to the science of human longevity is the natural model of centenarians. The objective of this study was to verify whether the previously determined risk factors for atherosclerosis and atherosclerosis-related diseases change with age and, finally, to establish the vitamin nutritional status role. We studied 54 centenarians (14 males and 40 females) aged between 100–107 years (mean age 102.6±1.8 years) living in Sicily (Italy), recruited via the Registry Office, and compared them with three control groups composed of subjects with different age ranges. Total plasma Hcy, folate, vitamin B12 and pyridoxal phosphate (PLP) levels were compared between the groups by the Student's t test. The comparison between centenarians and <65-year old, randomly selected individuals showed that in centenarians the mean value of serum creatinine levels was 18 μmol/l (p=0.000) higher, the mean total Hcy value was 22 μmol/l higher (p=0.000), the mean PLP value was 17.9 nmol/l lower (p=0.000), the mean folate level was 2.1 nmol/l lower (p<0.001) and vitamin B12 was 70.5 pmol/l lower (p=0.000). The comparison between centenarians and >65-year old, randomly selected individuals showed that in centenarians the mean value of serum creatinine levels was 8 μmol/l higher (p=0.037), the mean total Hcy value was 11.6 μmol/l higher (p=0.000) and the mean PLP value was 4.2 nmol/l higher (p=0.000). It seems that centenarians are protected by some mechanism (maybe genetic) that allows them a long survival despite the high value of homocysteinemia. On the other hand, it can by hypothesized that good vitamin intake is essential to live over 100 years. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) may be associated with a variety of autoimmune phenomena causing a therapeutic dilemma for treatment with interferon-α (IFNα), which stimulates autoimmune symptoms, or with corticosteroids, which may lead to an increasing of viral load. To evaluate the possible role of intravenous immunoglobulins (IVIg) in the response of patients treated with IFNα, we administered IVIg plus IFNα and compared the results with a group of patients treated with IFNα alone. Methods: Forty-two patients affected by chronic hepatitis C with probable autoimmune disease were eligible for this open-label, randomised study. All patients tested positively for anti-nuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies and anti-mitochondrial antibodies. Patients were randomly assigned to one of two groups: group A received IVIg at a dosage of 400 mg/kg each day for 5 days, and then 3 MUI of leucocyte IFNα three times a week, while group B received physiological solution followed by the administration of leucocyte IFNα three times a week at the same dosage for 6 months. Complete biochemical response was defined as a sustained normalisation of alanine aminotransferase levels, and complete virological response was defined as complete clearance of virus throughout the entire 6-month follow-up period. Immunological response was measured in terms of Autoimmune Hepatitis (AIH) score, while histological response was based on a reduction in histological activity index (HAI) score. Results: Compared with patients receiving IFNα alone, a higher percentage of patients who received IFNα plus IVIg showed complete virological and histological responses (p = 0.04). More patients in the combination therapy group achieved biochemical and immunological responses, although the differences between the groups were not statistically significant at all time points. Conclusions: Exogenously added Ig might modulate the immune network at various points. We propose that the immunomodulating action of IVIg acts synergistically with IFNα, achieving a better response to IFN treatment in patients with chronic HCV associated with autoimmunity. Data obtained from this preliminary study indicate a positive prospective for the clinical use of gamma globulins in patients with a high probability of autoimmune disorders associated with HCV infection. [ABSTRACT FROM AUTHOR]

Quality of life and behavioral functions are severely reduced in patients affected by Alzheimer’s disease (AD). Among the drugs employed in the treatment of this invalidating degenerative dementia, tacrine (THA) seemed to play a possible therapeutic role. Our study was aimed to evaluate the efficacy of THA in the treatment of AD, performing a comparison with lecithin and/or placebo treatment. Five randomized controlled trials on tacrine versus lecithin and/or placebo treatment were randomly selected. Mantel-Haenszel-Peto method was applied. Patients treated with tacrine achieved better results than control subjects (overall OR = 2.34; 95% CI 1.42–3.85); but long-term treatment with tacrine was not significantly more efficacious than placebo. Statistical significance in favor of THA versus other drugs employed was obtained in MMSE and ADAS-Cog tests in the studies carried out by Eagger et al. and Knapp et al. Moreover, Fitten et al. administered the highest tolerated THA dose to only a few patients enrolled in the study. The presence of broad CIs observed in the 5 meta-analytic studies infer non homogeneity of effects of treatment. Solely few patients improved, whereas the clinical conditions of the majority remained stationary. Between 5 and 10% of the outpatients in each single study presented reversible side effects calling for suspension of THA treatment. The optimal dose ranged between 80 and 160 mg THA, but often produced side effects. Comparative trials revealed the reduced efficacy and elevated toxicity of THA treatment, dampening the initial enthusiasm concerning the usefulness of this drug in AD. Furtermore, tacrine-induced side effects provoked many dropouts in all studies investigated. The effectiveness of tacrine treatment in AD disease was not fully confirmed. Other studies are required to identify doses and modalities of administration of this drug in AD. [ABSTRACT FROM AUTHOR]

Abstract: Stabbing headache is a relatively rare type of chronic “primary” headache with distinctive features with respect to more common forms of paroxysmal headache, such as cluster headache and trigeminal neuralgia. Drug treatment is empirical because of the lack of knowledge on the pathophysiology of stabbing headache. We examined 26 patients recruited over 10years, who met the diagnostic criteria for stabbing headache. Interestingly, more than half of these patients had autoimmune disorders, including multiple sclerosis, Sjögren''s disease, Systemic Lupus Erythematosus, Behçet''s disease, autoimmune vasculitis, and antiphospholipid antibody syndrome. We speculate that stabbing headache may develop as a result of neuroinflammation and, at least in some cases, may be an epiphenomenon of focal demyelinating lesions of the upper or lower brain stem. [Copyright &y& Elsevier]

The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-γ) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effector's mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile. [ABSTRACT FROM PUBLISHER]

Abstract: Non-melanoma skin cancers are a common reality worldwide. The principal cause that determines the occurrence of these diseases is the exposition of the sun, which principally causes an alteration in the immune system. Therefore, it is possible that other forms of innate or acquired alterations of the immune system could favor the occurrence of non-melanoma skin cancers. For example, several studies have demonstrated that immunosenescence creates an immunosuppressive state that encourages the development of malignances, and new discoveries have noted the importance of T cells and in particular of T regulatory cells (Treg) and T receptor CD28 in this mechanism. Similar results are obtained analyzing the effect of immunosuppressive drugs. The importance of the immune system and its alteration in the genesis of non-melanoma skin cancers is fundamental for the creation of a new therapeutic and less invasive approach. [Copyright &y& Elsevier]

Abstract: The increased incidence of malignancies in elderly patients living in industrialized countries has led to both identify the causes that alter the normal homeostatic balance in elderly and designate the specific treatments. The progressive decline of the immune system (immunosenescence) involving cellular and molecular alterations impact both innate and adaptive immunity. The immunosenescence leads to increased incidence of infectious diseases morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. Here, we summarize the knowledge on the major changes in the immune system associated with aging in primary lymphoid organs as well as a description of molecular mechanisms, and the impact on cancer development. [Copyright &y& Elsevier]

Purpose: Hepatorenal syndrome (HRS) is a pre-renal-like dysfunction that generally onsets in cirrhotic patients presenting ascites. We investigated the improvement of renal function in subjects with hepatorenal syndrome after terlipressin administration and the survival times after this treatment. Fifty-two patients affected by cirrhosis, with diagnosis of hepatorenal syndrome were treated with intravenous terlipressin plus albumin (group A) or with albumin alone (group B). Liver and renal function, plasma renin activity, and aldosterone plasma levels were monitored.Results: Patients from group A showed a significant improvement (p < 0.001) of renal function valued by creatinine rate compared with the results obtained in group B. The probability of survival was higher in the group A (p < 0.0001).Conclusions: Our results seem to confirm that the administration of terlipressin plus albumin improves renal function in patients with cirrhosis and type I HRS and that a reversal of hepatorenal syndrome is strongly associated with improved survival. [ABSTRACT FROM AUTHOR]

Abstract: The majority of cancers occur in adults over the age of 65, with about 70% of all cancer deaths in this population. Tumor lysis syndrome (TLS) is a complication of hematological and others malignancies, caused by massive tumor cell lysis due to chemotherapy, immunotherapy, radiotherapy. TLS can determine an alteration of the body''s normal homeostatic mechanisms and cause hyperuricemia, hyperkaliemia, hyperphosphatemia, hypocalcaemia and uremia. Aggressive fluid administration has been recommended in all patients presumed to be at risk of this syndrome. Hyperkaliemia has to be correct with hypertonic glucose, resins and dialysis. Initial treatment of hyperphosphatemia includes phosphate binders. The cornerstone of prevention and treatment of hyperuricemia includes both inhibiting the formation of uric acid as well as increasing its renal clearance through urinary alkalinization, allopurinol, rasburicase. Conventional management to prevent acute renal failure consists of intravenous hydration, diuretic therapy and urinary alkalinization. The management of TLS in elderly patients is often complicated by the renal and the heart senescence and by the presence of multiple co morbid conditions, polypharmacy and difficulties with adherence to complex medication and dietary regimens. [Copyright &y& Elsevier]

Background. Hepatocellular carcinoma is a major health problem worldwide and the third most common cause of cancer-related death. HCC treatment decisions are complex and dependent upon tumor staging. Several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Despite of only modest objective response rates according to the Response Evaluation Criteria in Solid Tumors, several studies showed encouraging results in terms of prolongation of the time to progression, disease stabilization, and survival. Cellular immunotherapy would improve the immune state and has potential in enhancing the therapeutic outcome for HCC patients. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” “molecular immunological targets,” “tumour-associated antigens,” “Tregs,” “MDSCs,” “immunotherapy.” Discussion and Conclusion. Treatment strategies combining blockade of immunoregulatory cell types such as Tregs and MDSCs and of inhibitory receptors, with vaccine-induced activation of TAA-specific T cells, may be necessary to achieve the most effective therapeutic antitumour activity in HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways. [ABSTRACT FROM AUTHOR]

The aim of our work has been to evaluate the different options of tracheoesophageal voice rehabilitation in over 70-year-old patients, who had undergone laryngectomy, assessing advantages and drawbacks of this method of vocal recovery. A retrospective study has been carried out. This has included 40 subjects, all aged more than 70 years old, who have been referred to tracheoesophageal voice rehabilitation. It has been realized a phonatory fistula between trachea and esophagus with prosthesis positioning by means of a primary puncture in 18 cases and it has been realized a secondary puncture in 22 cases. The results gathered in these patients were compared with data obtained from a group made of 39 patients, less than 70 years of age that therefore represented our control group. In primary tracheoesophageal puncture (TEP), the short-term success was 67 %, while in the 22 cases who underwent secondary TEP, the short-term success was 64 %. After 2 years from TEP, the long-term success was 82.5 %. In the control group, the short-term success was 65 % in primary TEP and 73 % in secondary TEP. After 2 years from TEP, the long-term success was 77 %. The evaluation of the results has shown the absence of a statistically significant difference both as regards complications incidence, during and after surgery ( p > 0.9) and as regards overall success ratio of prosthesis implants between the two groups ( p > 0.7). The possibilities of tracheoesophageal recovery of elderly patients do not show dissimilarities in comparison with the results in younger subjects. [ABSTRACT FROM AUTHOR]

Abstract: The development of cardiovascular pathologies is potentially connected to the surrounding environment, partly due to purely environmental factors, like exposition to pollutions, or anthropological ones, like the type of manual or stressing working activities. The relevant literature has already widely discussed the correlation between the acute and chronic exposition to atmospheric pollutants of different types and the pathogenetic events, such as the atherogenesis, thrombosis, and hypertension, The present study intends to verify this idea on a larger population exposed to different geographical conditions, comparing an agricultural village (Pachino-Siracusa) with an industrialized area (Augusta-Siracusa), both having identical sanitary services of basic importance. On the basis of the specific rates of hospitalizations, we compared the prevalence of cardiovasular pathologies in the resident populations. These studies confirmed the negative influence of the risk factors deriving from the environmental pollutions even on the cardiovascular aging, displaying an increased rate of hospitalization for angina pectoris, myocardial infarction and cardiac arrhytmias in the industrialized population. [Copyright &y& Elsevier]

Context: Studies on experimental animals have shown liver is a common target of chemical carcinogens; this might suggest that occupational exposure to chemicals is another risk factor for HCC. However, the relationship between occupation and liver cancer has not been extensively studied, with the exception of the known association between vinyl chloride and angiosarcoma of the liver. Evidence Acquisition: A MEDLINE and conventional search of the past 50 years of the medical literature was performed to identify relevant articles on incidence and mechanisms of HCC due to occupational exposure to chemicals. Several important edited books and monographs were also identified and reviewed. Results: While laboratory data clearly indicate that the liver is an important target of chemical carcinogenesis, epidemiological studies provide very limited evidence on occupational risk factors for HCC. Nevertheless, we found some case reports and epidemiological data showing a moderately increased risk of HCC development in people exposed to vinyl chloride, organic solvents, pesticides, polychlorinated biphenyls, and arsenic. Conclusions: Occupational exposure to chemicals may be another risk factor for HCC development, but the interpretation of currently available findings is limited by the small number of studies, questionable accuracy of the diagnosis of liver cancer, and potential confounding or modifying factors such as chronic hepatitis virus infection and alcohol consumption. Further relevant investigations are required for clarifying the actual contribution of occupational exposure to chemicals in HCC development. [ABSTRACT FROM AUTHOR]

Background: The impact of hepatitis B virus (HBV) vaccination campaigns on HBV epidemiology needs to be evaluated, in order to assess the long-term immunity offered by vaccines against HBV. Objectives: To evaluate the current status of anti-HBV vaccine coverage among healthcare workers (HCWs) in Southern Italy, and to determine the long-term persistence of antibodies to hepatitis B surface antigens (anti-HBs) in such a cohort of subjects. Patients and Methods: A longitudinal, retrospective seroepidemiological survey was conducted among 451 HCWs, who were working at or visiting, the Occupational Health Department of a city hospital, in Catania, Italy, between January 1976 and December 2010. Results: At the 30-year follow-up (mean follow-up 10.15 ± 5.96 years, range 0.74-30), 261 HCWs had detectable anti-HBs titers indicating a persistence of seroprotection of 89.4% (out of 292 anti-HBs positive results, three months after vaccination). An inadequate vaccination schedule was the strongest predictor of antibody loss during follow-up (OR = 8.37 95% CI: 5.41-12.95, P < 0.001). A Kaplan-Maier survival curve revealed that the persistence of anti-HBs 30 years after vaccination, was 92.2% for high responders, while it was only 27.3% for low responders (P = 0.001). Conclusions: A good level of seroprotection persisted in 57.9% of the subjects after 30 years. Factors related to this immunization status confirmed the importance of vaccinating HCWs early in their careers and ensuring an adequate vaccination schedule. However, with particular reference to the low rate of hepatitis B vaccine coverage among HCWs in Southern Italy, the implementation of a new educational intervention as part of an active vaccination program is needed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Statin, Beyond Hyperlipidemia Toward a Novel Agent for Hepatitis C," by Mahmoud A. khattab and colleagues that was published in a previous issue.

Background: Nonalcoholic fatty liver disease develops in patients with chronic hepatitis C. Interferon and ribavirin combination therapy is the standard treatment for chronic hepati­tis C, but if present, NAFLD can reduce the virological response to anti-HCV therapies. Objectives: We determined whether the addition of rosuvastatin to interferon and ribavirin improves the sustained virological response (SVR) and reduces steatosis. Patients and Methods: This study was a prospective, randomized, open-label trial. Between January 2004 and December 2007, 65 patients with chronic hepatitis (27 women and 38 men, mean age 48 years) aged 32-63 years (median 46 years) were consecutively enrolled. Patients were randomly assigned to receive leukocyte interferon alpha (3 MIU 3 times per week) plus ribavirin (1200 mg per day) for 12 months or interferon alpha and ribavirin at the same dosages plus rosuvastatin (5 mg per day). The primary endpoints were measurements in SVR, liver enzyme, cholesterol, triglyceride, CRP, glucose, and insulin levels; and Homa-IR, fibrosis, and steatosis scores. Results: After 12 months of treatment, we observed a significant improvement in SVR in 51% of patients who received interferon plus ribavirin plus rosuvastatin compared with 18% of relapsers (OR 1.52; 95% CI= 0.41-5.64; RR 1.13). There were 23 responders (69%) and 10 nonre­sponders (30%) (OR 1.38; 95% CI= 0.49-16.5; RR 1.11). When comparing interferon plus ribavi­rin group vs interferon plus ribavirin and rosuvastatin group after 12 months, we observed a significant difference in AST (85.70 vs.106.5.00 IU/ml) (OR 1.2; 95% CI= 0.29-4.94; RR 1.04; p<0.001), ALT (81.80 vs. 126.2 IU/ml) (OR 1.2; 95% CI= 0.29-4.94; RR 1.04; p<0.001), LDL-cho­lesterol (0.01 vs. 0.60 mmol/l) (OR 14; 95% CI= 3.98-49.16; p RR 2.96; <0.001), triglycerides (0.17 vs. 0.2 mmol/l) (OR 20; 95% CI= 4.94-80.89; RR 5.38; p<0.05), and Viremia (1.8 vs. 2.48 UI/ml, p<0.05). Mean fibrosis score decreased 0.10 vs. 0.50 (OR 4.5; 95% CI= 0.89-22.66; RR 1.5; p<0.05), and mean steatosis score declined 0.30 vs. 0.50 (OR 11.2; CI= 2.88-43.53; RR 2.75; p<0.001). Conclusions: In HCV patients with NAFLD, the addition of rosuvastatin to interferon and rib­avirin significantly reduces viremia, steatosis, and fibrosis without causing side effects. [ABSTRACT FROM AUTHOR]

Background: The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate.Methods: A literature search identified potential markers for hepatocellular carcinoma. These markers were analysed and justification was provided for these factors' inclusion to (or exclusion from) the markers of hepatocellular carcinoma (HCC). A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC," "Lens culinaris agglutinin reactive AFP (AFP-L3) and HCC," "Des-γ-carboxy prothrombin (DCP) and HCC," "Glypican-3 and HCC," "Chromogranin A and HCC," "Transforming growth factor β1(TGF) and HCC," "α-l-fucosidase (AFU) and HCC," "Golgi protein-73 (GP73) and HCC," "Hepatocyte growth factor (HGF) and HCC," "Nervous growth factor (NGF) and HCC."Conclusions: Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. Given the poor response to current therapies, a better understanding of the molecular pathways active in this disease could potentially provide new targets for therapy. However, AFP shows a low sensitivity, therefore other biomarkers have been developed to make an early diagnosis and improve patients' prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The diabetes mellitus of type 2 (DMT2) is a disease of the elderly with multifactorial pathogenesis, characterized by interactions of genetic variations suspect for diabetes, as well as of the longevity and aging genes. Since today it is still not possible to obtain the diagnosis with laboratory methods of clinical genetics, we tried to identify the subjects of risk of future diabetes on the basis of a combined measurement of glycemia, the glycosylated hemoglobin (HbA1c) and the waist circumference (WC). The studied population consisted of 2603 elderly subjects of 65–84 years of age, involved in the epidemiological study called ILSA (Italian Longitudinal Study on Aging). The subjects who displayed at the baseline an impaired fasting glucose (IFG) accompanied by HbA1c and WC values above the normal cut-points proved to be diabetic after a 3-year follow-up in 18.96%, while the subjects with normal fasting glucose (NFG) accompanied by normal HbA1c and WC values were found to be diabetic only in 1.34%. It means that the presence of abnormal values of these 3 parameters in the elderly does not allow the identification of the risks for future diabetes in the great majority of subjects. We conclude that the results of prospective studies may gain particular significance not only regarding the glycemia, but also the other 2 risk factors, if we wish to reach not only a predictive diagnosis of risk for diabetes, but also to prevent the chronic degenerative complications of it. [Copyright &y& Elsevier]

Human phagocyte-specific chitotriosidase (CHIT-1) is a chitinolytic enzyme associated with several diseases involving macrophage activation. Previous studies have demonstrated that a high activity of Chit could have widespread effects on atherosclerosis, cardiovascular disease and dementia. The 24-bp duplication in the CHIT-1 gene is associated with a deficiency in enzymatic activity. In this study, we attempted to assess whether CHIT-1 could be a plausible candidate gene responsible for human longevity. Therefore, we compared the distribution of the CHIT-1 polymorphism genotype in three different populations of the Mediterranean area (Italian, Greek and Tunisian) aged over 90 years. As a control group for each nonagenarian and centenarian, a 60–70-year-old subject was genotyped. We found that the heterozygote frequency for the 24-bp duplication in the CHIT-1 gene was not significantly different among the oldest old subjects of Mediterranean populations, whereas it was significantly different between oldest old subjects and control subjects, being highest among the oldest old subjects and lowest among control groups. In the oldest old group, no subject was observed to be homozygous for CHIT-1 deficiency. Moreover, the mean enzymatic activity in heterozygous oldest subjects was lower than that in the control group. These data indicate that the heterozygosis for a 24-bp duplication in the CHIT-1 gene could have a protective effect in human longevity. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed at verifying the International Diabetes Federation (IDF)-indicated criteria in the elderly, characterized by a decrease of several normal values, the neglected evaluation of those values with aging, and an eventual decision of an obligatory consideration of the visceral obesity as a sign of the metabolic syndrome (MS), the relative prevalence of Acute Myocardial Infarction (AMI) and stroke. The study involved 3038 elderly persons (65–84 years), covered by the Italian Longitudinal Study on Aging (ILSA): they were investigated for the diagnosis of MS, for the prevalence of AMI and stroke at the baseline, and after 3 years. We applied both the IDF-criteria and a new concept considering the age-dependent increase of several parameters in older subjects, the previous cardio–cerebrovascular complications, as well as the presence of other diseases being independent of those complications. The prevalence of AMI and stroke determined according to the IDF-criteria is not different significantly from the results obtained in either the elderly population with “normal” or increased waist circumference (WC), nor in subjects with MS or without MS. After a 3-year-follow-up quite similar results were found. From these results one can conclude that the diagnostic criteria of the IDF for the MS are not valid for the elderly population. We propose some criteria on the basis of which one can reveal systematically significant differences between the MS and the cardiovascular complications. Our conclusion is that it seems to be necessary to verify the validity of our proposed criteria on wider long-term epidemiological studies. [Copyright &y& Elsevier]

Abstract: The diabetes of the elderly subjects has two forms: diabetes of long duration, manifesting itself in younger or medium ages, and senile diabetes, appearing above the age of 65 years. The diabetes of the elderly has usually only modest symptoms: it is not ketosic, but in spite of this, in order to avoid the chronic-degenerative complications, it is important to maintain a good, even if not an optimal compensation. The therapeutic intervention cannot neglect a correct alimentary regime and a programmed physical activity in correlation with the clinical conditions of the patient. If the compensation is not achieved only with these tools, one can add oral antidiabetic treatments. In the elderly patients we usually observe primary or secondary failure of the oral antidiabetic treatments, and in such context we have to apply insulin treatment, even in cases of moderate glycometabolic decompensations. While we are waiting for the gene-therapy or the inhalatory insulin preparations, actually there are at disposal only the insulin analogs in rapid, slow and mixed forms. We propose two treatment schemes: (i) The first one consists of three administrations of rapid insulin with the meals, and on dose of slow insulin 2h after the last meal in the evening. (ii) The second scheme consists of one administration of rapid insulin at lunch, one administration of mixed insulin at dinner, with the addition of oral antidiabetics of peripheric action, in the morning and the evening. A better compliance can be obtained, being a fundamental aspect in the elderly diabetics, and a reduction of the number and severity of the hypoglycemia, which are the most important aspects in the elderly diabetes. [Copyright &y& Elsevier]

Background: Hepatic steatosis is a common presentation in patients with chronic hepatitis C. Interferon alpha exerts both antiviral and immunomodulating actions, and influences on lipid metabolism. The aim of our study was to test whether L-carnitine reduces steatosis in patients treated with interferon and ribavirin.Patients and Methods: A total of 70 patients were randomly assigned to receive either leucocyte IFN alpha at a dose of 3 MIU thrice a week plus 1,000 mg ribavirin per day for 12 months (group A) or IFN alpha and ribavirin at the same dose plus 2 g carnitine per day (group B).Results: Comparison of the two treatments showed significant differences between the mean values of the following parameters at the end of the treatment: ALT -68 vs -95 IU/ml (P < 0.05), total cholesterol 0.08 vs -0.91 mmol/l (P < 0.05) and triglycerides +0.25 vs -20 mmol/l (P < 0.05); and at the follow-up: AST -35 vs -65 IU/ml (P < 0.05) and ALT -55 vs -84 IU/ml (P < 0.05). All values were lower in group B (IFN + Ribavirin + Carnitine) than in group A (IFN plus Ribavirin). When comparing those patients treated with IFN + ribavirin with those treated with IFN plus ribavirin plus carnitine, the response at the end of the treatment was 48% vs 56%, and the sustained response 39% vs 46%, respectively.Conclusions: Combined treatment with L: -carnitine, ribavirin and IFN alpha resulted in greater antihyperlipidaemic effects and than with ribavirin and IFN alpha alone. The results of this study suggest that L: -carnitine may have a role among the reduction of steatosis strategies in patients with hepatitis C treated with IFN alpha and ribavirin. [ABSTRACT FROM AUTHOR]

Abstract: A study pool of 1549 normoglycemic elderly in the age range of 65–84 years, taken from the epidemiological Italian Longitudinal Study on Aging (ILSA), was constructed. The values of IR, %B and %S were analyzed using the homeostasis assessment model-2 (HOMA-2). In the subjects displaying normal values of several studied parameters such as the arterial blood pressure, total cholesterol (T-CH), high-density lipoproteins (HDL), and triglycerides (TG), the values of IR, %B and %S remained in the normal ranges (in average 1.66±1.11, 133.64±63.56 and 91.12±79.75, respectively). These latter values increase in the subjects who had altered values of the studied basic parameters listed above, and the increases were higher with the higher frequency of the altered parameters. The results seem to confirm the possibility that the normoglycemic elderly subjects having a compensatory insulin hypersecretion against the IR, may develop a type 2 diabetes or a metabolic syndrome. [Copyright &y& Elsevier]

Abstract: In 1998, the World Health Organization (WHO) accepted the diagnostic criteria proposed in 1997 by the American Diabetes Association (ADA) and confirmed that, independent of age, the fasting plasma glucose (FPG) level from and above 126mg/dl in the morning should be considered as diabetic, while subjects with FPG 110–125mg/dl have an impaired fasting glucose (IFG), compared with the normal fasting glucose (NFG) level (up to 110mg/dl). In a pool of 4492 elderly people (65–84 years), we assessed the significance and meaning of these new diagnostic criteria of diabetes. A 5-year follow-up was carried out, during which out of 4492 elderly subjects, 2750 were re-examined. As regards the diagnosis, we applied both the criteria of WHO (1985, 1998). At our first observation (1992), 13.1% were diabetic in the elderly group, if applying the WHO (1985) criteria, and 15.1% applying the ADA-WHO definitions. When re-analyzing the subjects with FPG of 126–139mg/dl after 5 years, it became evident that the diagnosis of diabetes is not stable in this group, because 50.7% of them displayed FPG<126mg/dl (14.5% IFG; 36.2% even NFG). It means that the significance of FPG and the conditions of diabetes are different in the elderly, as compared with the younger adults. Furthermore, the oral glucose tolerance test (OGTT) of 60 elderly subjects in the age range of 71–80 years, admitted in our day hospital, were considered. Among the subjects with an FPG 126–140mg/dl, the OGTT was of diabetic type in 90%, while among IFG and NFG subjects, it was in 50 and 10%, respectively. In conclusion, in elderly subjects with FPG of 126–140mg/dl, the diagnosis of diabetes is not stable and requires further confirmation. [Copyright &y& Elsevier]

Abstract: Authors have considered the prevalence of hypertension (HT), myocardial infarction (MI) and stroke (S), in elderly subjects with diabetes, impaired fasting glucose (IFG) and normal fasting glucose (NFG), respectively. A high occurrence of diabetes in elderly subjects has been found. MI and S were more frequent in diabetic group than in IFG and NFG ones. HT proved to be elevated in the total pool, especially in older olds, and with a higher prevalence among those with diabetes. A 5-year follow-up has been carried out. The index of survival for MI and S was lower in subjects with diabetes. The subjects affected by both MI and S displayed the worst index of survival in all the three categories considered, therefore, it can be stated that such an association is a determinant factor of mortality. [Copyright &y& Elsevier]

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by steatosis and periportal and lobular inflammation. The molecular mechanisms involved in the anomalous behavior of liver cells have only partially been disclosed. Human Chitotriosidase (Chit) is a member of the chitinase family that it is mainly synthesized by activated macrophages. We investigated chitotriosidase gene expression in Kupffer cells to determine the potential implication of this enzyme in the inflammation and in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis. METHODS: Seventy-five liver biopsies from 40 subjects with NASH, 20 with simple steatosis, and 15 controls were used to detect CHIT expression, tumor necrosis factor-alpha (TNF-α), alpha-smooth muscle actin (α-SMA), and lipid peroxidation. RESULTS: CHIT was expressed exclusively by Kupffer cells. The levels of CHIT expression were significantly higher in NASH patients than in simple steatosis patients and in the control group. In addition, we found that CHIT over-expression influenced hepatic stellate cells activation, as demonstrated by the significant correlation between CHIT and α-SMA expression in NASH patients. A significant correlation was observed also between CHIT, TNF-α and lipid peroxidation in both NASH and simple steatosis. CONCLUSION: These results suggest that CHIT over-produced by Kupffer cells may contribute to the progression of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Inflammation has been involved in the development of dementia in cerebrovascular diseases. To investigate the cellular activation of the peripheral immune system in patients with Alzheimer’s disease (AD) and vascular dementia (VaD), we determined the presence of IL-18 and TGF-β1 in the plasma by using ELISA. The levels of IL-18 and TGF-β1 were significantly elevated in patients with AD and VaD compared to non-demented, age-matched subjects. We found an inverse correlation between the levels of IL-18 and TGF-β1 in AD patients. In VaD patients, the correlation between IL-18 and TGF-β1 reached a borderline positive value. Whereas, in the non-demented, age-matched subjects, a positive correlation between IL-18 and TGF-β1 levels was observed. These findings indicate that IL-18 and TGF-β1 elevation is associated with AD and VaD patients, confirming that the immune system might exert a remarkable role in the development and progression of neurodegenerative disorders. Moreover, as different modifications were detected in the patients affected by AD and VaD, we propose that IL-18 and TGF- β1 plasma levels might represent possible differential biomarkers. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer is one of the most frequent tumors in men. The neuroendocrine differentiation in prostate cancer has become more widely recognized and has attracted considerable attention as a potentially new finding with major diagnostic, prognostic and therapeutic implications. We investigated the role of the serum concentrations of CgA in a group of 57 patients with prostate cancer and in 61 elderly subjects with benign prostate hyperplasia (BPH). Neuron-specific enolase (NSE) is the most frequently employed marker to detect neuroendocrine features. Serum prostate-specific antigen (PSA), CgA and NSE levels were determined. Comparing prostate cancer group versus BPH group, the CgA level difference was 63.00ng/ml (p <0.0001) and the PSA level difference was 50.86mcg/ml (p <0.0001). Between prostate cancer group and control group the CgA level difference was 94.3ng/ml (p <0.0001), the PSA level difference was 52.91mcg/ml (p <0.0001), and the NSE level difference was 1.34μg/l (p <0.0001). Patients with higher CgA levels had poorer prognosis and survival, compared to those with lower CgA levels. These results support the concept that serum CgA level determination before treatment is a potential prognostic factor for prostate cancer. [Copyright &y& Elsevier]

Inflammation has been reported to be involved in the pathogenesis of cerebrovascular dementias (CvDs). This study investigated the involvement of Chitotriosidase (ChT), a chinolitic enzyme mainly produced by activated macrophages, in the pathophysiology of Alzheimer's disease (AD) and ischemic CvD. In addition, the levels of interleukin (IL)-16, IL-18, transforming growth factor (TGF) -β1 and superoxide anion (O2–) were determined to evaluate the relationship between ChT levels, these cytokines and oxidative stress in both AD and ischemic CvD patients. The levels of ChT and IL-16, IL-18, and TGF-β1 mRNA were investigated using quantitative real-time polymerase chain reaction on macrophages of peripheral blood of 40 patients with AD, 40 patients with ischemic CvD and 40 non-demented age-matched subjects. The results show that ChT, IL-16 and O2– levels significantly increased in ischemic CvD patients compared with AD patients and were significantly and positively correlated with IL-18 and O2–. The production of IL-18 was increased in both AD and ischemic CvD patients. TGF-β1 expression was higher in AD patients and was inversely correlated with the expression of ChT, IL-16 and IL-18, respectively. In non-demented age-matched subjects no significant changes in ChT and IL-16, IL-18, and TGF-β1 expression were found. Our results indicate that ChT, IL-16, IL-18 and TGF-β1 are increased in ischemic CvD and AD, confirming that the immune system may play an important role in the development and progression of neurodegenerative disorders. In addition, the present findings suggest that ChT could also play a crucial role in pathological conditions such as CvD in which the inflammatory process is activated. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. Methods: Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. Results: In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was − 8.20 μmol/L (p =0.000); the difference in short-chain acylcarnitine − 2.60 μmol/L (p =0.029); the difference in soluble acid carnitine − 10.80 μmol/L (p =0.000); the difference in long-chain acylcarnitine − 0.40 μmol/L (p =0.036); and the difference in total carnitine −11.20 μmol/L (p =0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was −5.80 μmol/L (p =0.006); the difference in soluble acid carnitine − 7.20 μmol/L (p =0.000); and the difference in total carnitine − 7.50 μmol/L (p =0.000). Conclusion: Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients. [Copyright &y& Elsevier]

Objective The aim of this study was to examine the clinical picture of Parkinson's disease (PD) and vascular parkinsonism (VP) in the elderly, in an attempt to differentiate the clinical history, symptoms, signs and response to therapy. Material and methods Thirty-two elderly patients with late onset PD and 45 with VP were enrolled and the clinical features of two groups were compared. All patients underwent brain MRI and were scored using the Unified Parkinson's Disease Rating Scales (UPDRS) -II, -III. Results Patients with PD had a younger age at onset and a longer duration of the disease as compared to patients with VP. Nearly all PD patients showed a good response to levodopa therapy, while only 29% of patients with VP were responsive to levodopa treatment. Vascular risk factors as well as postural tremor, gait disorders and pyramidal signs with lower body predominance, were more frequent in patients with VP. Ninety-three % of PD patients had normal MRI, whereas all patients with VP had cerebral vascular lesions. UPDRS-II, -III scores at baseline were higher in VP than in PD patients and their increases throughout the follow-up period were more marked in VP than in PD patients. Conclusions Clinical history, symptoms, signs, response to therapy, and brain imaging help to differentiate PD and VP as two clinical entities with different clinical, prognostic and therapeutic implications, even if the coexistence of PD and a cerebral vascular disease in elderly patients is not infrequent and can make the diagnosis difficult. [ABSTRACT FROM AUTHOR]

Abstract: Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery. Although selective serotonin reuptake inhibitors (SSRI) are often used in post-stroke depression (PSD), it has been observed that only a subset of patients is responsive to this treatment. Other patients respond to tricyclic antidepressants or MAO inhibitors, which, however, may not have a favorable profile of safety and tolerability in post-stroke patients. In this double-blinded, placebo-controlled study, we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor, reboxetine, in a subset of PSD patients classified as affected by “retarded” depression. Reboxetine (4mg, twice daily, for 16 weeks) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke. We assessed the severity of depressive symptoms by the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). HDRS and BDI scores (mean±S.D.) at baseline were, respectively, 24±1.31 and 19.87±1.46 in the placebo group, 24.06±1.52 and 20.56±2.16 in the reboxetine group. After 16 weeks, HDRS and BDI mean scores were respectively 22.73±2.4 and 18.4±3.33 in the placebo group, 9.26±2.15 and 8.06±3.43 in the reboxetine group [p &#60;0.01 versus the respective baseline (paired t-test); # p &#60;0.01 versus retarded depressed patients treated with placebo (one-way analysis of variance (ANOVA) applied to the difference from baseline, associated with Dunnett''s t-test to isolate the differences)]. Reboxetine showed a good efficacy, safety and tolerability in PSD patients affected by “retarded” depression. We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with “retarded” depression. [Copyright &y& Elsevier]

Background/Aims: Non-alcoholic steatohepatitis (NASH) is a disorder that is histologically characterized by macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and fibrosis. NASH can range from a benign condition to end-stage liver disease. The mechanisms promoting transition from steatosis to NASH appear to involve multiple cellular adaptations to the oxidative stress occurring when fatty acid metabolism is altered. We evaluated the relationship between lipid peroxidation and other oxidative stress biomarkers with changes in expression of heme oxygenase-1 (HO-1) in human hepatic steatosis ranging from simple steatosis to NASH. Methods: HO-1 expression, lipid peroxidation, ferritin and GSH levels were assayed from liver biopsies obtained from 60 subjects: 35 with NASH, 15 with simple steatosis and 10 controls. Results: The HO-1 expression was significantly increased in NASH patients and the increase reflected the severity of the disease. A significant correlation was observed between the increased levels of HO-1 and ferritin, and between the increased levels of HO-1 and lipid peroxidation. Moreover, NASH patients with lower levels of GSH exhibited higher expression of HO-1. Conclusions: The induction of HO-1 is an adaptive response against oxidative damage elicited by lipid peroxidation and it may be critical in the progression of the disease. [Copyright &y& Elsevier]

Antidepressants are used to treat chronic daily headache disorders such as migraine and chronic tension-type headache (TTH), which are often associated with depression and anxiety. Here, we studied the efficacy and tolerability of amitriptyline and citalopram, given alone or in combination, in patients with ‘triple’ comorbidity of depression, TTH, and migraine. Eighty-eight patients were enrolled in the study and randomly divided into two groups. The first group received amitriptyline and the second citalopram for 16 weeks. Patients were assessed at weeks 0, 4, 8, and 16. The two drugs were equally efficacious in relieving depressive symptoms, although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks. Patients who did not respond to monotherapy (<30% of improvement in the clinical scores) were treated with a combination of the two drugs for 16 additional weeks. In these selected patients, the combined treatment produced a substantial improvement in depression, migraine and TTH without producing major side effects such as those commonly related to the ‘serotonergic’ syndrome. The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH, migraine and comorbid depression that do not respond to monotherapy. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rationale and objective. Depression is a significant complication of stroke. The effectiveness of antidepressant drugs in the management of post-stroke depression (PSD) has been widely investigated. However, the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies. Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by anxious depression or retarded depression. Methods. This was a randomized double-blind study. Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table. Randomisation was planned so that 50% of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50% were assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score depressive symptoms. Results. Both citalopram and reboxetine showed good safety and tolerability. Citalopram exhibited greater efficacy in anxious depressed patients, while reboxetine was more effective in retarded depressed patients. Conclusions. Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in centenarians compared to the other groups. There was a negative correlation between age and axial length (transverse diameter), age and width and age and common bile duct (CBD) diameter in the elderly group only. Conclusions: The study of gallbladder function in elderly people and centenarians is important because this parameter is related to the quality of digestion and absorption of many alimentary substances as well as to the formation of cholesterol gallstones. We found that gallbladder functions in centenarians are almost normal with respect to the elderly and adults. Contractility was higher than in our elderly sample. This fact ensures a correct concentration of bile salts and a good intestinal transit rate. It may represent one of the factors allowing for good digestive function in these subjects, which contributes to their health status. [Copyright &y& Elsevier]

Purpose: Only early detection of non-symptomatic patients is able to arrest the diffusion of the non-symptomatic HCV infection and lead to prompt treatment. Our aim was to attempt to correlate the presence of perihepatic lymph nodes and hepatitis C infection and to assess whether ultrasonography can have a role to promote specific investigations for pre-clinical diagnosis of virus C infection. Method: We performed a controlled study on a cohort of 7974 subjects from a town of 27 000 inhabitants on the eastern coast of Sicily. Serologic hepatitis A, B and C markers, alanine aminotransferase levels and abdominal ultrasound examination according to size and number of peri-hepatic lymph nodes were performed on blind basis. Results: One or more pathological lymph nodes were present in 684/7974 subjects. Haematochemical tests revealed the presence of anti-HCV positivity in 528/684 subjects with pathological lymph nodes and in 8/7290 subjects without pathological lymph nodes, there being a significant difference (P<0.0001) between the two groups. Conclusion: Our results confirm the association between perihepatic lymph nodes and virus C infection. Correct diagnostic assessment of this datum could lead not only to early diagnosis by specific blood test for HCV and consequent prompt aimed treatment, but could pave the way for efficacious territorial prevention and detection of an elevated percentage of likely non-symptomatic carriers. [Copyright &y& Elsevier]

Aim: Levocarnitine is an important contributor to cellular energy metabolism. This study aims to evaluate the effects of levocarnitine supplementation on body composition, lipid profile and fatigue in elderly subjects with rapid muscle fatigue. Method: This was a placebo-controlled, randomised, double-blind, two-phase study. Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study. Prior to randomisation all patients entered a 2-week normalisation phase where they were given an ‘ad libitum’ diet, according to the National Cholesterol Education Program (Step 2). Subjects were asked to record their daily food intake every 2 days. Before the 30-day treatment phase, subjects were randomly assigned to two groups (matched for male/female ratio, age and body mass index). One group received levocarnitine 2g twice daily (n = 42) and the other placebo (n = 42). Efficacy measures included changes in total fat mass, total muscle mass, serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo)A1, and apoB levels. The Wessely and Powell scale was used to evaluate physical and mental fatigue. Subjects were assessed at the beginning and end of the study period. Results: At the end of the study, compared with placebo, the levocarnitine-treated patients showed significant improvements in the following parameters: total fat mass (-3.1 vs -0.5 kg), total muscle mass (+2.1 vs +0.2 kg), total cholesterol (-1.2 vs +0.1 mmol/L), LDL-C (-1.1 vs -0.2 mmol/L), HDL-C (+0.2 vs +0.01 mmol/L), triglycerides (-0.3 vs 0.0 mmol/L), apoA1 (-0.2 vs 0.0 g/L), and apoB (-0.3 vs -0.1 g/L). Wessely and Powell scores decreased significantly by 40% (physical fatigue) and 45% (mental fatigue) in subjects taking levocarnitine, compared with 11% and 8%, respectively, in the placebo group (p < 0.001 vs placebo for both parameters). No adverse events were reported in any treatment group. Conclusion: Administration of levocarnitine to healthy elderly subjects resulted in a reduction of total fat mass, an increase of total muscle mass, and appeared to exert a favourable effect on fatigue and serum lipids. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein (LDL) oxidation in vivo depends on lipid composition and on plasma antioxidant status. The aim of our study was to investigate the relationship between plasma lipid composition and LDL oxidation and, in particular, to explore whether LDL-cholesterol/triglycerides ratio (LDL-C/TG) and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio (LDL-C/HDL-C) can be used as predictive parameters of LDL oxidation in vivo. In 87 volunteers over a wide range of age plasma lipids and LDL oxidation were studied. Blood was collected after 12 h overnight fast. LDL oxidation was estimated by the level of conjugated diene (BDC) in the lipid fraction isolated from plasma after gradient ultracentrifugation. The results were expressed as µmol/I (BDC/I) to evaluate the level of oxidized LDL, and as nmol of BDC for mg of LDL-cholesterol (BDC/LDL-C) for the evaluation of LDL oxidation degree. BDC/I correlated significantly with age, total and LDL-C, apolipoprotein B and TG, while BDC/LDL-C negatively correlated with total cholesterol, apolipoprotein B, LDL/TG and LDL/HDL ratios. Age of subjects significantly correlated with total and LDL-C and apolipoprotein B. TG have a significant inverse correlation with HDL-C. Our results support the hypothesis that among the several factors involved in LDL oxidation the most important determinants are LDL/TG. Plasma triglycerides appear to be very important even when circulating cholesterol levels are within normal limits. Moreover, we found that the LDL/HDL ratio is also very important with regard to the putative protective role of HDL against LDL oxidation in vivo. In conclusion, plasma lipid parameters must be evaluated not only for their absolute values but also for their mutual ratios as expression of plasma lipid homeostasis. Both LDL/TG and LDL/HDL ratios can be used as predictive parameters of in vivo LDL oxidation. [ABSTRACT FROM AUTHOR]

Background: Low circulating plasma levels of total homocysteine (tHcy) are associated with a lower prevalence of coronary heart disease among black people than among white people living in Burkina Faso.Objective: The purpose of this study was to provide a rationale for a possible mechanism for the decrease in plasma tHcy levels among black people compared with white people living in Burkina Faso.Methods: Healthy, black, adult, lifelong inhabitants of Burkina Faso and healthy, white adults born in Italy but living in Burkina Faso ≥5 years were eligible for enrollment. Controlled diets were assigned to all subjects for 2 weeks before the study. After an overnight (12-hour) fast, a methionine-loading test was performed in all subjects. Plasma levels of tHcy, cysteine, glutathione, and cysteinylglycine were measured simultaneously using high-performance liquid chromatography after fasting (baseline) and at either 4 and 8 hours (n = 30) or 2, 4, 6, and 8 hours (n = 4) after methionine loading. During the 12 hours after loading, the clinical conditions and adverse events of subjects were monitored. Results were analyzed using the Student t test and Mann-Whitney U test.Results: Seventeen black adults (9 males, 8 females; median age, 21 years) and 17 white adults (8 males, 9 females; median age, 35 years) were enrolled. Mean plasma levels of tHcy, cysteine, and glutathione increased from mean baseline levels more slowly in the black group than in the white group and peaked 8 hours after methionine loading (16.8 ± 3.0 μmol/L, 130.4 ± 25.7 μmol/L, and 68.3 ± 21.2 μmol/L, respectively). In the white group, these levels peaked 4 hours after loading (16.1 ± 4.0 μmol/L, 215.8 ± 18.6 μmol/L, and 38.6 ± 12.4 μmol/L, respectively). Only the mean plasma cysteinylglycine level decreased significantly (from 35.7 ± 11.4 μmol/L to 19.0 ± 6.1 μmol/L; P < 0.01) in the black group after 4 hours. This decrease was followed by an increase after 8 hours (29.6 ± 12.0 μmol/L). In the white group, a less remarkable change in mean cysteinylglycine level was observed, with a peak after 4 hours (16.3 ± 4.3 μmol/L).Conclusions: The findings of this study suggest that, in addition to lower plasma tHcy levels, the metabolism of plasma tHcy is different in black people than in white people after methionine loading. This difference may be due to different alimentary habits associated with a reduced dietary availability of methionine. Moreover, the higher plasma levels of glutathione before and after methionine loading appear to occur exclusively in black people compared with whites and correspond with the variation of cysteinylglycine, suggesting that, in addition to nutritional factors, a racial component may contribute to the difference in plasma levels of tHcy. This difference also might explain, in part, the lower prevalence of coronary heart disease in black people living in Burkina Faso compared with that in other populations. [Copyright &y& Elsevier]