A multidisciplinary therapeutic approach for reducing the risk of psychiatric side effects in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin.

GOALS: To evaluate the effectiveness of psychiatric counseling in reducing the rate of development of psychiatric side effects of antiviral therapy with interferon-α and ribavirin among study participants compared with standard clinical monitoring alone. BACKGROUND: Interferon-α is used to treat chronic hepatitis C. Interferons may induce adverse events that usually, but not always, reverse within a few days after the end of therapy. STUDY: Two hundred eleven patients with chronic hepatitis C, genotype 1b were treated with peginterferon and ribavirin for 48 weeks in a prospective trial. Two groups were randomly created. Group A was interviewed by a team of gastroenterologists, psychiatrists, and psychologists and treated with psychotherapy once a month. Group B was monitored once a month according to a conventional protocol that did not include psychotherapy. SVR (sustained viral response), severe psychiatric symptom onset, and mood progression were assessed (P calculated using Fisher exact test, Friedman test, Dunn posttest, and Mann-Whitney U-test). RESULTS: At baseline, there was no difference in depressive symptoms or liver histologic score between the 2 groups. The onset rate of severe psychiatric manifestations was 4.7% (Group A) and 16.1% (Group B) between the 24th and 36th weeks (P<0.01). Fifteen participants in Group A and 39 in Group B required antidepressants and benzodiazepines (P<0.05). CONCLUSIONS: Patients can develop depressive symptoms during interferon therapy. Multidisciplinary medical treatment with psychiatric counseling provided during the treatment of chronic hepatitis C may contribute to the decrease or prevent the higher rates of depression associated with interferon treatment.

Effects of vascular risk factors on balance assessed by computerized posturography in the elderly.

AIMS: The purpose of this study was to evaluate the effects of vascular risk factors, isolated or in association, on balance, as assessed by posturographic platform. METHODS: One hundred and seven elderly subjects (mean age 73.8+/-5.8), with no cognitive impairment (MMSE>24), able to perform self-care activities and to walk independently for at least 400 meters, free from major diseases. Subjective complaints were assessed by means of the Sickness Impact Profile Questionnaire. The following cardiovascular risk factors were considered: hypercholesterolemia, smoking, hypertension, glucose intolerance, and obesity. Balance tests were performed in three standardized positions (side-by-side, semi-tandem, tandem) on a vertical force platform, from which center of foot pressure positions and displacements were recorded. RESULTS: A large percentage of enrolled subjects (35.5%) complained of unsteadiness, dizziness or vertigo, but only a few (24=22.4%) reported at least one fall in the 6 months before enrolment in the study. Among the cardiovascular risk factors taken into account, only glucose intolerance and, to a lesser extent, obesity, were associated with worse performance in stabilometric tests, independent of age and sex. Subjects with 3 or more risk factors, compared with those with 2 or less showed worse performance in medio-lateral sway (p=0.001), track length (p=0.05) and elliptical area (p=0.005), in tandem position. CONCLUSIONS: The cumulative presence of cardiovascular risk factors may contribute to impairment of balance in the elderly. This effect may be due to subclinical damage of that part of the nervous system controlling balance.

Effects of hypertension on balance assessed by computerized posturography in the elderly.

Unsteadiness, dizziness and vertigo occur more frequently in hypertensive subjects, compared to the normal ones. This study evaluated the influence of hypertension on balance tests, performed on posturographic platform. The study pool consisted of 112 persons aged 65 and older (65 hypertensives), their mean age was 72.9+/-0.5, scored on the Mini Mental State Examination (MMSE) greater than 24, were able to perform self-care activities, to walk independently for at least 400 m and were free from major diseases. Subjective dizziness and vertigo were assessed by means of Sickness-Impact-Profile-Questionnaire (SIPQ). The static posturographic tests were performed on a vertical force platform, from which the center of foot pressure (COP) positions and displacements were recorded. In balance tests three standardized positions were utilized: feet 30 degrees apart, semitandem and tandem. Subjects with hypertension complained more frequently dizziness and vertigo (41.5% vs. 21.3%). The track-length and COP-velocity were associated with age in all the balance tests. In semitandem and tandem positions, the medio-lateral sway distance significantly increased in elderly subjects compared to young controls. No difference, however, was found in balance tests between normotensive and hypertensive subjects. Those with uncomplicated hypertension compared with normo-tensive subjects, although complaining more frequently symptoms of postural instability, did not show worse performances in static posturographic tests.

From chronic low back pain to disability, a multifactorial mediated pathway: the InCHIANTI study.

STUDY DESIGN: Clinicoepidemiologic study in the Chianti area (Tuscany, Italy). OBJECTIVE: To evaluate whether performance measures of lower extremity function confounds the association of low back pain (LBP) with self-report disability in specific basic and instrumental activities of daily living (IADLs). SUMMARY OF BACKGROUND DATA: LBP is high prevalent in older population and has a negative impact on functional status. Studies on the pathway leading from LBP to disability are limited and often the role played by important confounders is not considered. METHODS: A total of 956 InCHIANTI study participants aged 65 and older able to complete performance-based tests of lower extremity function were included in this analysis. LBP was defined as a self-report of back pain "quite often-almost every day" in the past 12 months. Lower extremity function was evaluated administering the Short Physical Performance Battery. In addition, participants were asked to walk on a 7-m course and collect an object from the ground. Depressive symptoms (CES-D score), trunk flexion-extension range of motion, and hip-knee-foot pain were also considered in the pathway from LBP to disability. RESULTS: Compared with participants who did not report LBP, those with LBP were more likely to report difficulty in performing most activities of daily living. LBP was also associated with disability in the activities of bathing, doing the laundry, performing heavy household chores, cutting toenails, shopping, and carrying a shopping bag. The association between LBP and disability in selected ADLs and IADLs was no longer statistical significant, after adjustment for performance in lower extremity function, with exception of the activity of "carrying a shopping bag". CONCLUSION: The cross-sectional association between LBP and self-reported disability, in specific tasks is modulated by performance measures. Specific performance-based tests that explore the functional consequences of LBP may help design specific interventions of disability prevention and treatment in patients with LBP.

Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus.

To assess whether pathogenic endothelial dysfunction is involved in acute idiopathic tinnitus we enrolled 44 patients and 25 healthy volunteers. In blood from the internal jugular vein and brachial vein we determined malonaldehyde, 4-hydroxynonenal, myeloperoxidase, glutathione peroxidase, nitric oxide, L-arginine and L-ornitine, thrombomodulin (TM) and von Willebrand factor (vWF) activity during tinnitus and asymptomatic period. Higher plasma concentrations of oxidative markers and L-arginine, and lower nitric oxide and L-ornitine levels were observed in jugular blood of patients with tinnitus, there being a significant difference between brachial and jugular veins. TM and vWF activity were significantly higher in patients' jugular blood than in brachial blood. Our results suggest oxidant, TM, vWF activity production are increased and nitric oxide production reduced in brain circulation reflux blood of patients with acute tinnitus. These conditions are able to cause a general cerebro-vascular endothelial dysfunction, which in turn induce a dysfunction of microcirculation in the inner ear.

Markers of inflammation, vitamin E and peripheral nervous system function: the InCHIANTI study.

BACKGROUND: Aging of the peripheral nervous system is associated with several morphologic and functional changes, including a decrease of the nerve conduction velocity. There is evidence that these changes contribute to age-related-decline in muscle strength, sensory discrimination, and autonomic responses. The aim of this study was to characterize the decline in nerve conduction velocity in the peripheral nervous system over the aging process and to identify factors that, independent of age, affect nerve conduction velocity. METHODS: We measured motor nerve conduction velocity of the right superficial peroneal nerve using a standard neurophysiologic technique in a population-based sample of subjects aged between 20 and 103 years old enrolled in the InCHIANTI study. RESULTS: Average conduction velocities in the peripheral nerve decreased linearly with age in both sexes. We found that diabetes, cognitive impairment, uric acid, sIL-6R and alpha-tocopherol were significant predictors of nerve conduction velocity independently of the potential confounding effect of age, sex, sex x age interaction term, height, lymphocytes, neutrophils number, alpha1 and alpha2-globulin serum protein. CONCLUSIONS: Our findings are consistent with the hypothesis that inflammation and inadequate antioxidant defenses are associated with accelerated decline of nerve conduction velocity over the aging process.

Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls.

BACKGROUND: Increased generation of reactive oxygen species (ROS) and oxidative stress may be of crucial importance in the pathogenesis of endothelial damage. Furthermore, there is understood to be a relationship between endothelial damage, glycemic control, disorders of lipid metabolism, and coagulative hemostatic disorders. OBJECTIVE: This study investigated within- and between-group changes in various circulating markers of oxidation-reduction balance and endothelial function after a balanced moderate-fat meal with and without antioxidant supplementation in patients with early-stage, untreated type 2 diabetes mellitus; subjects with impaired glucose tolerance (IGT); and healthy controls. METHODS: In this single-blind, controlled clinical study, groups of patients with type 2 diabetes and subjects with IGT were identified and compared with a group of healthy controls. All groups followed a controlled, well-balanced diet for 10 days before and throughout the study. Before and after consumption of a standardized moderate-fat meal, plasma levels of oxidants (malondialdehyde, 4-hydroxynonenal, oxidized low-density lipoprotein), the antioxidant glutathione peroxidase, and markers of endothelial function (NO, endothelin-1, von Willebrand factor [vWF], vascular cell adhesion molecule-1 [VCAM-1]) were determined. These measures were then reassessed after 15 days of standard antioxidant treatment consisting of a thiol-containing antioxidant (N-acetylcysteine 600 g/d), a bound antioxidant (vitamin E 300 g/d), and an aqueous phase antioxidant (vitamin C 250 mg/d). The efficacy of antioxidant treatment in reversing abnormalities in oxidation-reduction balance after a moderate-fat meal was assessed by evaluating changes in plasma levels of ROS on the morning of the 16th day following an overnight fast. Safety was monitored in terms of adverse events, vital signs, physical findings, and laboratory values. RESULTS: The study included 46 patients with type 2 diabetes (23 men, 23 women; mean [SD] age, 41 [3] years; mean body mass index [BMI], 24 [2] kg/m(2)), 46 with IGT (23 men, 23 women; mean age, 39 [3] years; mean BMI, 23 [3] kg/m(2)), and 46 control subjects (23 men, 23 women; mean age, 40 [1] years; mean BMI, 22 [1] kg/m(2)). Before supplementation, all 3 groups had significantly increased levels of oxidants, vWF, and VCAM-1 (all, P < 0.001) and significantly decreased levels of antioxidants and NO (both, P < 0.001) after consumption of a moderate-fat meal. After 15 days of antioxidant treatment, significant improvements in these measures were seen in all groups (P < 0.05). CONCLUSIONS: This study showed changes in oxidation-reduction balance, NO bioavailability, and nonthrombogenic endothelial factors after a moderate-fat meal in patients with type 2 diabetes and those with IGT, but these postprandial changes were reverse in all subjects after 15 days of standard antioxidant supplementation. These findings suggest that the use of anti-oxidants may have decreased oxidative stress in these subjects.

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients.

OBJECTIVE: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (> or = 65 years). STUDY DESIGN: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg. RESULTS: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was -24.0/-13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP < or = 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP > or = 10 mmHg or in supine systolic BP > or = 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3-M15), whatever the previous treatment received during the 3-month, doubleblind period (M0-M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported. CONCLUSION: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years-80 years with systolo-diastolic hypertension (SDH) or ISH.

IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors.

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.

Can ultrasonographic findings of perihepatic lymphadenopathy promote investigations to detect possible presence of virus C infection in non-symptomatic subjects?

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 27000 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.

Serum IL-1beta levels in health and disease: a population-based study. 'The InCHIANTI study'.

Interleukin-1 plays a role in normal homeostasis and in the inflammatory response which is deemed to be responsible for the development of major chronic diseases that are highly prevalent in the elderly. Aim of this study is to evaluate the factors influencing the serum levels of Interleukin-1 beta, in a large and representative population. Data were from the InCHIANTI project, a study of factors contributing to the decline of mobility in late life, which sampled people living in two sites in the surroundings of Florence. Blood samples were obtained from 1,292 participants and frozen aliquots were stored at -80 degrees C. The serum levels of several cytokines were measured by enzyme linked immunosorbent assay using an ultrasensitive commercial kit. Interleukin-1 beta serum levels were associated with congestive heart failure (p > 0.001) and angina (p = 0.02), with Ca2+ serum levels (p = 0.02), and with a history of dyslipidemia (p = 0.05). We found no association between serum IL-1beta level and age, sex, consumption of cardioactive drugs and serum levels of IL-1Ra, IL-6, sIL-6R, IL-10 and TNF-alpha. Our data could lend support to the hypothesis that IL-1beta is mainly involved in the functional alterations of cardiomyocytes under conditions marked by mononuclear cell infiltration and by downregulation of calcium.

Controlled clinical trial to assess the response of recent heroin abusers with chronic hepatitis C virus infection to treatment with interferon alpha-n2b.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is the most common infectious disease among heroin abusers, but it is recommended that specific treatment with interferon be delayed until at least 6 to 12 months after the end of drug addiction. OBJECTIVE: We investigated the response of heroin abusers to interferon treatment shortly after the end of detoxification treatment with methadone. METHODS: We studied 2 homogeneous groups of white Italian patients with chronic HCV infection: former male heroin abusers and males without a history of drug addiction. Tumor necrosis factor, interleukin-1beta, interleukin-2, activated monocytes, anti-HCV antibodies, HCV RNA, and alanine aminotransferase levels were assessed. Standard treatment was initiated with 5 MU interferon alpha-n2b administered subcutaneously once daily for 8 weeks. Patients with negative HCV-RNA findings at the end of 8 weeks received further treatment with 5 MU TIW subcutaneously for an additional 48 weeks. RESULTS: Thirty of 47 patients in group A (former heroin abusers) and 30 of 30 patients in group B (controls) completed the study. Heroin abusers presented a significantly enhanced response to treatment compared with the controls. After 8 weeks, HCV-RNA test results were negative in 27 of 30 patients in group A (90.0%) and in 25 of 30 in group B (83.3%) (P = NS). Onset of relapse occurred significantly later in heroin abusers (mean [SD], 53 [3] weeks) than in controls (26 [2] weeks) (P < 0.05). Cytokine levels and activated CD11 antigen-expressing monocytes were significantly (P < 0.001) higher in heroin abusers than controls. CONCLUSION: Heroin abusers with chronic HCV infection were successfully treated with interferon alpha-n2b soon after the end of detoxification treatment.

A hyperdynamic portal syndrome with ascites after endoscopic laser treatment.

Laser therapy has gained wide acceptance and application in many medical disciplines. Side effects of laser therapy are rare and the most frequent mainly involve the skin. We describe a patient affected by familial adenomatous polyposis that had been repeatedly controlled and treated endoscopically using an Nd:Yag laser. He presented with a progressive hyperdynamic portal syndrome with ascites caused by some arterovenous fistulas. We hypothesize that a rare side effect of the laser treatment may have caused ischemic and coagulative tissue inflammation that triggered off the pathological communications between the arterial and portal circulation.

Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients.

Cognitive functions display a progressive impairment with ageing, and this is thought to be due to the accumulation of neuronal loss or acute and/or repeated microvascular accidents. Chronic damage to the brain cortex lead to decreasing ability of elderly subjects to cope with daily events and ultimately result in loss of self-sufficiency. Since proinflammatory cytokines have been implicated both in cerebrovascular injury due to atherosclerosis and in Alzheimer's disease (AD), we investigated 70 elderly subjects with neurocognitive and functional impairment. Diagnosis was established in 54, the others were included in the "mixed" group. Sera were collected and stored at -70 degrees C until measurement of IL-1beta and TNF-alpha, performed by commercial ELISA kits. Data obtained were analysed with respect to other socio-demographic, psychoneurological and clinical variables. The results show that serum TNF-alpha was lower in mild-moderate AD compared to severe AD and dementias due to vascular disease, as well as the TNF-alpha/IL-1beta ratio. Both cytokines showed a significant relationship with age. Our study suggests that proinflammatory cytokines serum profiles seem to discriminate between mild-moderate AD and vascular or mixed forms of dementia. Furthermore, it offers new evidence of a strong implication of inflammatory mechanisms in atherosclerosis, more than in less severe AD.