Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Levels of hexachlorocyclohexanes in agricultural environment of Sacco river valley.

Aim of this trial was to verify the occurrence and the distribution of hexachlorocyclohexanes (HCHs) in soil, sediment, straw, alfalfa, other animal feed grown in farms with contaminated soil. In the present study two years of monitoring activity in the province of Roma and Frosinone was reported. Experimental trial in two contaminated sites was carried out on uptake and translocation of HCHs in maize and alfalfa. In 19 sites soil, forage and weed has been collected for two years, soil samples consisted in cores of 40 cm to test the presence of HCHs at different deep. The analytical determinations in soil and plant samples were carried out by gas liquid chromatography with electron capture detector and confirmed by mass detector. In the first year (2005- 2006) 68% of soil samples were contaminated (HCHs > LOQ) and 3% of vegetable samples. In the second year (2006- 2007) 42% of soil samples resulted positive and 26% of vegetable matrix. In particular B hexacyclohexane was detected in wheat stem (0.037 mg/kg) with a soil contamination of 0.039 mg/kg and in alfalfa (0.012 mg/kg) with presence in soil of 0.004 mg/kg. Experimental trials on maize evidenced a translocation factor for this isomer stem/soil of 0.006 mg/kg ? and for grain of 0.005 mg/kg. On alfalfa translocation factor root/soil was 0.01 and shot/soil 0.009. A propose to calculate the threshold value of soil contamination to admit crop grown destined to animal feed, would be based on HCHs LOD values weighted with translocation factor.

Preliminary note on potential use of forage crops for soil phytoremediation of dieldrin.

The aim of this trial was to evaluate the feasibility of using tall fescue (Festuca arundinacea) and alfalfa (Medicago sativa) for phytoremediation of dieldrin. Experimental trial was carried out in greenhouse with temperature and light control. Each tested crop were seeded in individual pots (10 plants/pot) filled with contaminated soil (47 microg/kg dieldrin) and uncontaminated soil collected in sites located in the province of Latina (Italy). Samples of soil, root, and aerial part of plants were analysed at 3 and 6 months after seeding. The analytical determinations in soil and plant samples were carried out by GLC-ECD and confirmed by GLC-MS. After 6 months in the greenhouse, recoveries of dieldrin from soil planted with tall fescue and alfalfa were significantly lower than recoveries in unplanted control soil. Dieldrin residue values in root did not differ between the two different sampling times for each forage crop tested, but they were always higher in fescue than in alfalfa. Residue levels in aerial part were low (< 10 microg/kg) in the two forage crops. Preliminary results seem to confirm the ability of tested plants to enhance dissipation of dieldrin in soil at low level of contamination.

Uptake of organochlorine pesticides by zucchini cultivars grown in polluted soils.

Aim of this trial was to verify the occurrence and the distribution of organochlorine pesticides (OCPs) in zucchini cultivated varieties grown in glasshouses and in open field with different levels of pollutants in soil. Residues of OCPs have been detected in soils and crops in the province of Latina, an intensively agricultural area of Lazio Region, in Italy. The study has been focused at crop harvest in less contaminated glasshouses and during crop life cycle in contaminated field in spring-summer time. Dieldrin distribution in different part of plant is similar among zucchini cultivars grown in contaminated field. In crop grown in field and in glasshouses with soil pollution >0.01 mg/kg, we found dieldrin in all zucchini fruits and flowers, at the same level or higher than the maximum residue limit (RML) fixed by European law for edible vegetables (0.02 mg/kg). Instead in soil with pollution < or = 0.01 mg/kg total OCPs it would be possible to grow zucchini cultivars.

Distribution of organochlorine pesticides in crop growing in the province of Latina.

Aim of this trial was to verify the occurrence and the distribution of organochlorine pesticides (OCPs) in soil, uptake and translocation by different crops growing in glasshouses with different level of pollutants. Residues of OCPs have been detected in soils and crops in the province of Latina, an intensively agricultural area of Lazio Region, in Italy. Dieldrin was quantified particularly in zucchini, cucumber, melon, tomato during a vegetation period. Sampling was carried out at three different times after transplanting. Roots, stem, Leaves and fruits were analysed separately. It would not be advisable to grow cucurbits in soil with OCPs residues > 0.100 mg/kg, to respect the RML admitted in UE in cucurbitaceous fruits.

Fungicide residues in pears and apples after post harvest treatments by drencher.

Aim of this trial was to verify the residues of two fungicides, already authorised for the use in field (the admitted maximum limit of residues have been fixed), after post harvest treatments on pears and apples for defence against main post harvest rots. The use of formulation in post harvest must consider also the technique of product application. In fact there are different systems to carry out the treatments for the protection of the commodities during cold storage. In this trial two formulations of pyrimethanil and imazalil were applied by drencher on pome fruit.

Fungicide residues in pears, apples and grapes after post harvest treatments by thermonebulization.

In the context of trials conducted in cold store, in order to investigate efficacy of fruit protection applying agrochemicals, the fate during the storage of two active ingredients (a.i.): pyrimethanil and imazalil, have been studied. The experimental trials were done on eight varieties of apples and pears and two of grapes. Only field use of named pesticides was already authorised on fruits and maximum residue limits (MRL) fixed. In the present biennial experimentation (apples and pears in the first year; grapes in the second one). Two fungicides formulations were applied and treatments have been executed by thermonebulization technique. The storage cell, had a volume of 110 m3 filled up with the fruits until 80% of its capacity. Each fruit variety constituted one thesis of 4 replicates. For each trial, only one treatment was performed at the beginning of conservation period (72 days for pears and apples, and 57 days for grapes). In order to estimate fungicides persistence, residues determinations have been carried out. From results obtained especially on grape, not homogenous residues distribution on treated commodities was observed. For all theses, residue level has not evidenced statistically significant decrement as function of time, behaviour not as observed in field tests. The following average values of residues have been determined: in apples and pears, 0.7 mg/kg of imazalil much lower than 5 mg/kg (RML fixed for field use), and 1.2 mg/kg of pyrimethanil little higher than 1 mg/kg (RML fixed for field use); in grapes 0.5 mg/kg pyrimethanil much lower than 3 mg/kg (RML fixed for field use).

Joint sonography in asymptomatic patients with HCV correlated hepatitis.

OBJECTIVES: Many different articular symptoms may appear in patients with HCV hepatitis, but in a relatively large number of patients no rheumatic symptoms are present. This sonographic study was undertaken to detect the possible presence of early articular changes in HCV patients without any rheumatic manifestations. METHODS: The knee, hip and shoulder were evaluated in a cohort of 29 consecutive HCV patients without any rheumatic symptoms. Results were compared with those obtained by the evaluation of 29 healthy subjects who were negative for markers of HCV and HBV infections. RESULTS: Results showed the presence of alterations in 96.5% of the patients, with significant differences in comparison to controls (p < 0.0001). Slight inflammatory changes were found in all the joints examined. The knee was involved in 79.3% of the cases, the hip in 27.6% and the shoulder in 89.6%. CONCLUSIONS: Our preliminary study shows the presence of joint changes in the majority of cases. To the best of our knowledge this is the first ultrasonographic study to focus on joint evaluation in patients with HCV hepatitis. Broader epidemiological and virological investigations, in particular for the HCV subtype and HLA genotype, will be required to elucidate the relationship between HCV infection and rheumatic symptoms.

Presence of plant protection products in three agricultural areas of Regione Lazio.

Aim of the research was to verify the impact of plant protection products on three significant agricultural areas of Regione Lazio: Maccarese, Cisterna di Latina, Sabaudia-Terracina. This research studied the presence of some active ingredients, indicated by technicians as distributed, on soil, water, crop and air samples, the last one in greenhouse; the analysis, carried out by multi-residue methods, allowed to investigate also on a large amount of active ingredients not indicated by technicians. The determinations have been obtained, using internal standards, by GC-NPD, GC-ECD, HPLC-UV, HPLC-DAD, with different columns, conditions and wavelength of adsorption. Taking into account the results we could to assert that only a small part of the molecules searched were found in the samples and that they are typical for the crops and the environment treated. In greenhouse, more persistence was founded in wood greenhouse, treated from the outside, probably for the release of a.i. in time from wood and for a better distribution. The active ingredients more frequently founded must be controlled to avoid possible accumulation or leaching, especially for herbicides in the areas of Maccarese and Cisterna di Latina. Furthermore, the molecule on which more attention must be done when applied, are: linuron on carrots, penconazole on zucchini and cymoxanil, often used inappropriately, particularly on minor crops, like red-radish. Although the number of sampling was limited, it has been possible to outline the situation in the three zones considered, for directing choices, that could be more sensible at sanitary spin-off and at the environment.

Increased soluble P-selectin levels in hepatitis C virus-related chronic hepatitis: correlation with viral load.

BACKGROUND: Platelet functional abnormalities are commonly found in patients with chronic liver disease; however, their nature and clinical significance are still a matter of discussion. METHODS: Soluble P-selectin (sP-selectin, a marker of in vivo platelet activation) levels, lipid pattern, and clotting activity were investigated in 39 patients with histologically confirmed chronic C hepatitis. RESULTS: Serum factor VIIc (P < 0.01), total cholesterol (P < 0.005), high density lipoprotein (P < 0.001), and low density lipoprotein (P<0.05) levels were lower in patients compared with healthy subjects, whereas triglyceride and fibrinogen levels were similar in both groups. Platelet counts were lower in chronic hepatitis patients compared with controls (P < 0.0001), and approximately 20% of patients had thrombocytopenia (platelet counts < 110 x 10(3)/microL). Platelet-associated immunoglobulin G (PAIgG) was present in 30.8% of patients. Plasma sP-selectin levels were higher in hepatitis C patients compared with controls (P < 0.0001), and significant differences were observed with respect to the Scheuer score (P < 0.01). The analysis of the distribution of plasma sP-selectin showed the presence of higher levels in patients with low platelet counts compared with patients with normal platelet counts and controls (P < 0.0001); moreover, sP-selectin levels did not correlate with the presence of PAIgG. On the other hand, sP-selectin levels directly correlated with serum hepatitis C virus (HCV)-RNA (P < 0.05) and inversely correlated with platelet count, blood lipids, and factor VIIc. CONCLUSIONS: The results obtained in this study support the hypothesis that HCV infection might be directly responsible for a condition of in vivo platelet activation in patients with chronic C hepatitis.

Morphologic left ventricular patterns and prevalence of high-grade ventricular arrhythmias in the normotensive and hypertensive elderly.

In the elderly, systemic hypertension is the main risk factor for cardiovascular diseases. Left ventricular hypertrophy, the most common adaptation to chronic pressure overload, has been recognized as an independent risk factor for an increased incidence of sudden death and arrhythmic disturbances. This study compared the prevalence of serious ventricular arrhythmias in elderly individuals with uncomplicated hypertension and in normotensive age-matched controls, using left ventricular mass index (LVMI) to differentiate patterns of anatomic adaptation to systolic, diastolic, or systolic-diastolic hypertension. The study enrolled 378 consecutive untreated elderly subjects (> or = 65 years of age), without clinical evidence of heart failure; 203 were hypertensive and 175 were normotensive. Each participant underwent standard 12-lead electrocardiography, M-mode and B-mode echocardiography, and 24-hour ambulatory electrocardiographic monitoring. Serious, statistically significant arrhythmias (Lown classes > or = 3) were present in 6.8% of normal subjects versus 17.1% of individuals with systolic, 31.5% of those with diastolic, and 20.4% of participants with systolic-diastolic hypertension. Arrhythmias did not differ in terms of left ventricular morphologic patterns or LVMI or between subgroups of hypertensive patients. Our data support the hypothesis that the pathogenesis of arrhythmias is related not to the electrophysiologic derangement of hypertrophied muscle but, rather, to the effects of hypertension on the cardiac structure. Cardiac fibrosis, one of the deleterious events accompanying hypertension, may be the main substrate for ventricular arrhythmias.

Natural history of cardiac involvement in myotonic dystrophy (Steinert's disease): a 13-year follow-up study.

Myotonic dystrophy (MD) is associated with a wide spectrum of cardiac abnormalities, but only a few longitudinal studies have investigated the natural course of heart disease in MD. To assess whether neuromuscular involvement significantly predicts cardiac disorders in MD, 83 patients with various grades of disease severity were enrolled in a 13-year follow-up study (mean, 60.6 +/- 37.8 months) that included periodic physical and instrumental cardiac examinations (standard and Holter electrocardiography, echocardiography). During follow-up, muscular disease worsened clinically in 9 patients (11%) whose baseline severity grade changed accordingly; only 3 of them demonstrated parallel worsening of cardiac disturbance, however, compared with a large number of patients who showed additional cardiac abnormalities. These included further worsening of pre-existing pathologic features (19/83) and the appearance de novo of serious arrhythmias and/or conduction defects (23/83). Pacemaker implantation was necessary in 11 of 83 patients (13.2%) who had symptomatic bradyarrhythmias, bifascicular block, and P-R prolongation with a His-to-ventricle interval exceeding 55 ms, as documented by electrophysiologic study. Eight (9.6%) patients died: 2 from noncardiac and 1 from unknown causes, 1 from heart failure, and 4 from sudden death closely related to documented ventricular tachycardia. The incidence and seriousness of arrhythmic and conduction disturbances correlated with the severity of the muscular involvement. Nevertheless, cardiac and muscular disease did not show a linear progression. Cardiac involvement generally worsened more rapidly than did skeletal muscle disease.

Peripheral neuropathy without cryoglobulinemia in patients with hepatitis C virus infection.

BACKGROUND: An association between essential mixed cryoglobulinemia and hepatitis C virus infection has been documented by many reports. Some clinical manifestations such as purpura, arthralgia, vascular lesions and peripheral neuropathies are also connected with the presence of detectable cryoglobulins. The association between HCV infection, the presence of mixed cryoglobulinemia and peripheral neuropathy is well documented. The aim of this study was to define the possible presence of peripheral neuropathy in HCV patients without detectable cryoglobulins and the possible association with the different genotypes. METHODS: Twenty patients (11 females, 9 males) with chronic HCV hepatitis and without detectable cryoglobulins were submitted to neurological and electrophysiological studies to detect a possible peripheral neurological involvement. In all patients the HCV infection was assumed by the presence of antibodies to HCV with ELISA assay and then confirmed with recombinant immunoblot assay. HCV genotyping was obtained by INNO LIPA in 15 out of 20 patients. In 4 patients a sural nerve biopsy was possible. RESULTS: Genotype 1b was present in 80% of patients, while 1a in 13.3% and 4 in 6.6%. Thirteen patients had positive neurological anamnesis (65%), while neurological examination was positive in 40% of the cases. Electromyographic study was positive in 50% of subjects. The sural nerve biopsies agreed with axonal degeneration in amyelinated fibres. CONCLUSIONS: Our results suggest a possible peripheral neurological system involvement in patients with HCV infection without cryoglobulins.

Adrenomedullin assay and its clinical significance.

Adrenomedullin (Am) is a recently discovered peptide, first purified from pheochromocytoma specimens, with a chemical structure similar to that of CGRP and amylin. Adrenomedullin is present in numerous human body tissues and its powerful vasodilatatory activity is thought to play an essential role in cardiovascular and renal homeostasis.

CGRP and ET-1 plasma levels in normal subjects.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide displaying about 50% homology with amylin which is secreted from the pancreatic islets of Langerhans. The main form, the beta-CGRP, is produced by the enteric nervous system and perivascular nerves of the vasa-vasorum. It represents one of the most powerful vasodilator yet discovered but its role is not yet completely clarified. High levels of this peptide have been shown in patients affected with thyroid medullary carcinoma, phaemocromocytoma and lung carcinoma. Recently circulating levels of CGRP have been found in normal subjects. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, isolated from porcine endothelial cells, is an important regulator of the vascular tone acting in physiological antagonism with atrial natriuretic hormone (ANH). With this study we intended to investigate the presence of any correlation between CGRP and ET-1 in normal subjects. PATIENTS: For the study we considered 20 normal subjects (11 males and 9 females) aged 23 to 50. MEASURES: Plasma levels of CGRP and ET-1 were measured by radioimmunological Kit. RESULTS: A positive and significant correlation between calcitonin gene-related peptide and endothelin-1 was found. CONCLUSIONS: Our results confirms that CGRP and ET-1 have opposing actions on vessels and that they can act together in haemodinamic regulation.

[Vasodilation in cirrhosis: is CGRP (calcitonin gene-related peptide) also among the possible mediators?]. / La vasodilatazione del cirrotico: fra i possibili mediatori anche il CGRP (peptide correlato al gene della calcitonina)?

According to cirrhotic patient's hyperkinetic circulatory state and to different pathophysiologic moments of kidney and liver failure, it is suggested that in cirrhosis a vasoactive balance is changed to more active vasodilatation. Also calcitonin gene-related peptide (CGRP) is likely involved in this change.

[Tolerability and side effects of interferon alpha in the treatment of chronic viral hepatitis]. / Tollerabilità ed effetti collaterali dell'interferone alfa nel trattamento delle epatiti croniche virali.

It is reported a review on side effects and toxicity of alfa interferon in treatment of chronic viral hepatitis. The clinical experience in 44 patients affected by chronic hepatitis and treated with 3MU of alfa interferon is analysed.

[Nephrotoxicity of drugs]. / Nefrotossicità da farmaci.

Setting out from the high prevalence of iatrogenic toxic effects on the kidney, the authors examine the pathophysiological mechanisms underlying this toxicity, and suggest their classification. The principal pathophysiologic and clinical models of the action of various groups of drugs responsible for these effects are discussed.