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Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population., Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l., Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD., Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes.

Background: Few studies have been performed to explore parameters that influence liver stiffness measurement (LSM) using transient elastography in general population., Aim: To explore factors influencing LSM in healthy and in subjects with non-alcoholic fatty liver disease (NAFLD)., Methods: LSM was performed in a well-characterized cohort of subjects aged between 30 and 63 years. After exclusion of any causes of liver disease, the healthy cohort was defined and was compared with participants with NAFLD. The 95th percentile value of LSM in healthy was used as a cutoff suggesting relevant fibrosis., Results: Among 780 subjects evaluated, 331 were defined as healthy. The median value was 4.4kPa (3.7-5.2) and the 95th percentile was 6.8kPa. LSM was not influenced by gender, age, anthropometrics and biochemical parameters. Only insulin resistance was independently associated with increasing of LSM. In the cohort of 157 subjects with NAFLD, LSM was higher than in healthy (5.6±1.9 vs 4.6±1.3kPa; p<0.001). On multivariate analysis, the degree of steatosis was independently associated with increasing of LSM in NAFLD cohort (β=0.271; 95% CI=0.026-0.095; p<0.001). Participants with diabetes and/or severe steatosis had the highest probabilities of relevant fibrosis., Conclusions: LSM varies between 3.7 and 5.2kPa in healthy Caucasians and is influenced only by insulin resistance. In NAFLD, severe steatosis and diabetes are factors influencing LSM., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.

Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50-60% of atypical mast cells (MCs). She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings) and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

An educational program, consisting in a clear explanation of the technical aspects and use of the adrenaline auto-injection devices (AAD) and in a practical test utilizing a demonstration kit was given to 350 patients from our outpatient clinic. AAD was also distributed to 50 patients formerly followed by another allergy clinic without training. At practical control test, only 10% of the untrained patients where able to correctly use the AAD versus 80% of trained subjects. Since AAD is a life-saving procedure in severe anaphylactic episodes, this attempt to improve the ability of the patient to comply with the procedure can improve the efficacy of the treatment and eventually the patient's health.

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly named Churg Strauss Syndrome, is a multisystem disorder characterized by chronic rhinosinusitis, asthma, and prominent peripheral blood eosinophilia; it is classified as a vasculitis of the small and medium sized arteries, although the vasculitis is often not clinically apparent in the initial phases of the disease. We present the case of a woman with EGPA who was frequently treated with high dose steroid therapy during hospital admission for refractory asthma. After December 2008, the date when we started Omalizumab, we observed a significative reduction of circulating eosinophils and IgE serum level, and the patient was no more hospitalized for respiratory failure or asthma attacks.

Aim: The prevalence of systemic reactions (SR) to Hymenoptera stings in children was estimated in values lower than 1% in early studies but much higher in recent surveys. We evaluated the current prevalence and the incidence of SR and large local reactions (LLR) to Hymenoptera stings in children in Italy., Methods: The data on children were collected from the database of the population study on the city of Cotignola, analyzing the answers to the part of the questionnaire about Hymenoptera stings, that concerned if the subject was ever stung by apids or vespids, if there has been a SR or a LLR, and if subjects with reactions received a diagnostic evaluation and a medical treatment., Results: Of the population of 1035 children, 173 (16.7%) were stung at least one time by Hymenoptera. Of them, 5 had had a SR and 9 had had a LLR. This defines a prevalence of SR of 0.5% and of LLR of 0.9%. Only one reaction was severe. Of the 14 subjects with SR or LLR, 5 (35.7%) underwent a diagnostic evaluation and one (7.1%) was treated with venom immunotherapy. The incidence of SR in the subsequent 2 years was 0.09% in the first year and 0.08% in the second year., Conclusions: These findings do not confirm the recent reports of an increased prevalence of Hymenoptera venom allergy in children. The incidence of SR to stings, thus far unreported for children, was very low both in the first and in the second year.

Background: Most cases of beer allergy reported so far have been associated with hypersensitivity to the non-specific lipid transfer protein (LTP). In view of the marked differences in brewing processes we assessed IgE reactivity as well as tolerance to many different beers in an allergic patient., Methods: A 45 year-old man hypersensitive to grass pollen, cat dander and Alternaria tenuis with a history of urticaria and dyspnoea after drinking beer and a weak skin reactivity to commercial corn extract was studied. The patient underwent SPT with 36 different brands of beer and an open challenge with those scoring negative was performed. An immunoblot analysis was carried out using 2 SPT-positive beers, 2 SPT-negative beers, and barley, wheat, and maize extracts using both patient's serum and a maize LTP-specific in-house developed polyclonal antibody from rabbit. Further, the immune reactive LTP of one beer was separated by HPLC and the chromatogram was compared to that of purified maize LTP., Results: Beer SPT scored positive in 30/36 cases. The immunoblot analysis showed IgE reactivity at about 10 kDa against the two SPT-positive beers and against maize with both patient's serum and the polyclonal anti-LTP rabbit serum, whereas the two SPT-negative beers, and barley extract scored negative. The immunodetected protein co-migrated with maize LTP., Conclusion: In beer-allergic patients the diagnostic workup may point to the detection of some tolerated products that can be consumed risk-free., (© 2012 John Wiley & Sons A/S.)

A 39-years-old man afferred to our hospital for a fever lasting for more than 6 months, without abnormalities at physical examination (in particular no skin alterations); a recent laboratory and instrumental investigation was ineffective and so a fever of unknown origin (FUO) was diagnosed Since he reported an history of infantile mastocytosis (usually auto-resolving) we evaluated his serum-tryptase levels that resulted of 49 ug/L (normal value 20 ug/L), raising the doubt of the presence of an active mastocytosis. The following bone marrow evaluation showed aggregates of CD117 positive cells and a c-Kit point mutation at codon D 816V confirming the diagnosis of indolent mastocytosis.The present case confirm that FUO can be caused by an otherwise asymptomatic indolent mastocytosis, thus suggesting to include the serum-tryptase level measurement in the diagnostic approach to this pathological condition, at least in selected cases.

Background: The worldwide prevalence of allergic diseases such as rhinitis, asthma, and atopic dermatitis is continuously increasing, while other allergic disorders such as urticaria and angioedema are less investigated. We performed a population study evaluating the prevalence of any kind of allergic disorders., Methods: The entire population of 7,201 inhabitants of Cotignola (Ravenna, Italy) was surveyed by a questionnaire assessing symptoms related to rhinitis, asthma, anaphylaxis, skin symptoms and insect sting allergy as well as the features of clinical presentations, diagnosis, and treatment received., Results: Valid questionnaires were obtained by 6,676 inhabitants (92.7%). The sample was formed by 3,266 males and 3,495 females, the mean age was 45.6 years; 1,035 subjects (15.5%) were aged less than 18 years; 404 subjects (6%) had at least one episode of wheezing/breathlessness in their lifetime, and 243 of them (60.1%) had a diagnosis of asthma; 1,002 subjects (14.8%) had nose symptoms in their lifetime, and 375 of them (37.4%) had a diagnosis of allergic rhinitis or rhinoconjunctivitis. For other allergic manifestations, data were obtained from 5,730 subjects; of them, 178 (3.1%) had skin symptoms, 59 (1.1%) had oral symptoms, and 37 (0.6%) had anaphylaxis; 207 (3.6%) had reactions to insect stings. There were no significant differences in prevalence between Italians and immigrants. Only 51.7% of subjects with asthma, 46.5% of those with rhinitis, 22.7% of those with other allergies, but 97.1% of those with insect allergy, received treatment., Conclusions: These findings confirm recent data on epidemiology of allergic diseases in Europe, particularly in Italy, and add some details on how such diseases are managed.

Background: Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid proved to be well tolerated, safe and effective in patients with respiratory allergy. Standard administration regimens are expected to require a long time before clinical benefit can be appreciated. We investigated whether pre-seasonal and perennial regimens differently affect the clinical efficacy of grass pollen SLIT., Methods: Adult patients with allergic rhino-conjunctivitis with/without mild intermittent asthma due to grass pollen were included into this open prospective study and randomised to receive SLIT with a continuous regimen (Group 1: 1,000 AU/week for the entire study period) or a pre-seasonal regimen (Group 2: 5,000 AU/week for 10 weeks/year for 2 years), or on demand drug therapy alone (Group 3) for two years. At entry (November 2005), at the end of the first and second pollen season, a Visual Analogue Scale (VAS) was used to assess patients' well-being. Symptom score and drug consumption were evaluated during the seasons. Methacholine challenge was performed at study entry and conclusion. Adverse events were recorded along the whole study duration., Results: Thirty-two patients were divided into Group 1 (n = 10), Group 2 (n = 11) and Group 3 (n = 11). A significant VAS improvement was observed in both SLIT groups, after the first and second pollen season, compared to baseline and to Group 3 (p < 0.05). Less symptoms and need for medications resulted during the second season (p < 0.05). No relevant variations in bronchial hyper-reactivity have been observed between the three groups. Only 2 patients experienced local or mild reactions in SLIT groups., Conclusion: Both pre-seasonal and continuous regimen of SLIT with monomeric allergoid turned out effective and safe, suggesting that a pre-seasonal course with 5,000 AU/week for 10 weeks may represent a convenient option in patients with grass pollen allergic rhinitis with/without mild intermittent asthma. Further research is urgently needed to consolidate these preliminary evidences.

We describe a case of worsening paraparesis induced by spinal cord compression at T6-T7 levels associated with compensatory extramedullary haematopoiesis from a compound heterozygote for haemoglobin E and for β-thalassemia. An emergency T3-T9 laminectomy was performed with excision of the masses and complete rehabilitation of the patient.

Objective: Ultrasonography is the first examination performed for screening of hepatocellular carcinoma (HCC); contrast-enhanced ultrasonography (CEUS) can help discriminate between HCC and other lesions. Primary hepatic lymphoma (PHL), even if rare, should be considered in the differential diagnosis of focal liver lesions (FLLs). Few data are available in the literature about the role of CEUS in the diagnosis of PHL; we tried to determine whether CEUS could have a role in this setting., Methods: we describe 2 cases of primary non-Hodgkin lymphoma of the liver associated with hepatitis B virus (HBV) infection. The first patient was a 62-year-old man who was an HBV-inactive carrier, and the second was a 58-year-old man with type 2 diabetes and chronic HBV hepatitis., Results: in both cases, ultrasonography showed a hypoechoic liver lesion (4 and 3 cm, respectively) with irregular margins in segment 4 of the liver. On CEUS, these lesions were inhomogeneously hyperenhanced in the arterial phase and hypoenhanced in the portal and late phases. Contrast-enhanced computed tomography (CT) in both patients showed slight hyperenhancement in the arterial phase and hypoenhancement in the remaining phases. Needle biopsy showed marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in both patients., Conclusions: Contrast-enhanced ultrasonography and CT did not help us differentiate PHL from HCC; in fact, in both cases we saw the characteristic findings of primary HCC. Primary hepatic lymphoma is a rare condition, but it should always be considered in the differential diagnosis of FLLs. We stress the important role of liver biopsy when imaging indicates HCC in patients without underlying cirrhosis.

Hepatitis C virus (HCV) infection affects about 3% of the world's population and often leads to chronic liver disease. In some industrialized countries, HCV prevalence increases with age, but the optimal management of older patients has not been accurately defined. HCV infection can also lead to lymphoproliferative disorders, the most common being mixed cryoglobulinemia (MC), and also for this condition that frequently affects elderly patients, the optimal therapeutic strategy is still debated. We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines. The patient underwent a treatment with interferon and ribavirin. Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms. After the end of treatment, HCV replication relapsed, but cryoglobulinemia and cutaneous symptoms did not recur. In the absence of definite treatment guidelines in this particular context, our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

In literature it has been described a high risk of systemic reaction after blood-sucking Dyptera bites, like mosquitoes and horsefly, in people sensitive to hymenoptera. A 51 year old man, allergic to hymenoptera venom and with a history of i.v. reaction after Mueller, who has been treated with Vespula sp. ITS for the last 3 years, was stung by a yellow, black and green insect on the neck. Five minutes after the bite, he suffered generalized hitching and urticaria, oral cavity and lower limbs paresthesia, followed by lost of consciousness. At the Emergency Room he was successfully treated with adrenaline, intravenous antihistamines and corticosteroid. The description of the insect as well as the lack of the sting on the site suggested a wasp as the culprit. By studying one of these insect that has been captured by the patient, it turned out it wasn't a Vespula, but a horsefly, the Tabanus bovinus, which resembles Hymenoptera. Skin prick test and RAST for Tabanus confirmed the allergology diagnosis. In conclusion, also Tabanus bovines can cause systemic reaction up to anaphylactic shock.

Background: Natural rubber latex allergy is a condition at high risk of anaphylaxis during surgery. However, latex contains several protein allergens and not all of them may show the same clinical relevance., Objective: To investigate the clinical relevance of Hey b 8, the natural rubber latex profilin., Methods: Seven patients without a clinical history of latex allergy but identified as being latex hypersensitive by positive SPT (3/7) and or positive latex-specific IgE during routine pre-surgery allergy investigations were studied. All patients were monosensitized to Hev b 8 (Hevea brasiliensis latex profilin) as shown by the detection of specific IgE to recombinant latex allergen components. Ten subjects with a history of latex allergy (urticaria, asthma, and/or rhinitis), sensitised to latex allergens other than profilin were enrolled as controls. Both patients and controls underwent a latex glove-wearing test; in case of a negative test, patients underwent surgery in a normal surgical setting., Results: All 7 patients scored negative on latex glove wearing test and underwent major surgery (orthopaedic, Caesarean section, pilonidal sinus, vascular, tonsillectomy, uterine revision, and uretral surgery) in a normal (non-latex safe) surgical setting without any consequence. In contrast, 9/10 (90%) controls showed a positive latex glove-wearing test (p < 0.01)., Conclusion: Latex profilin is either clinically irrelevant or is no longer present in latex products. This study highlights the importance of a component-resolved diagnosis of latex sensitisation as a tool to get a more precise assessment of the risk and to reduce the costs of healthcare.

Purpose: Hepatic hydrothorax is defined as the accumulation of pleural effusion in a cirrhotic patient in the absence of pulmonary or cardiac disease. Peritoneal fluid can pass into the pleural space through diaphragmatic fenestrations. The demonstration of such passage is important to establish the diagnosis of hepatic hydrothorax and can be achieved by intraperitoneal injection of nuclear contrast agents. Our aim was to evaluate the ability of contrast enhanced ultrasound in the detection of peritoneal-pleural communications., Materials and Methods: Seven patients with cirrhotic ascites and pleural effusion were studied in order to make a diagnosis of hepatic hydrothorax. SonoVue was injected into the peritoneal cavity (9.8 mL), and the peritoneal and pleural cavities were monitored by ultrasound. All patients were then studied using a nuclear scan., Results: Passage of SonoVue from the peritoneal to the pleural cavities was seen in 5 patients. In 2 patients, no passage of contrast agent was detectable. Nuclear scan was consistent with contrast enhanced ultrasound in all patients., Conclusion: This study shows that the presence of peritoneal-pleural communications can be demonstrated by real time contrast enhanced ultrasound, whose results are comparable to those of nuclear scan. Contrast enhanced ultrasound is cheaper and could theoretically be performed wherever ultrasound facilities are available.

Here are two cases of two male patients of 57 and 62 years of age, already known as allergic to stinging hymenoptera venom, who after a horsefly bite have presented a serious 3-4 degree-type Mueller classification systemic reaction. The diagnosis has been carried out clinically and after an accurate environmental anamnesis and along with prick tests and RAST, further specific entomological confirm. In literature the so called wasp-mosquito-syndrome has been indicated where hyaluronidase has been referred to as the cross allergen, between the hymenoptera venom and the mosquito saliva, which likely triggers the reaction. We believe that it is also possible to take into consideration a wasp-horsefly-syndrome as well, supposing the increased risk of anaphylactic reactions to Tabanidae bites, relatively frequent in areas with animals and streams, in subjects sensitized to stinging hymenoptera. We also suggest the possibility that in these subjects some systemic reactions are due in fact to Tabanidae bites and not so much for the failure of a possible active ITS of stinging hymenoptera.

Background: The glycoprotein CD30 is expressed and released by T lymphocytes that secrete type 2 helper cytokines of (T(H)2). These molecules play a role in the pathogenesis of allergic diseases. Venom immunotherapy has proven to be very effective in hymenoptera venom allergy through a shift in cytokine production from T(H)2-type cytokines to T(H)1-type cytokines., Objective: To evaluate the relationship between the soluble form of CD30 (sCD30) and venom immunotherapy in patients with hymenoptera venom allergy., Materials and Methods: sCD30 levels were assayed by enzyme-linked immunosorbent assay in the sera of 61 healthy controls and 14 patients with hymenoptera venom allergy who had undergone immunotherapy before treatment and 1,3, and 12 months after treatment started. Nine patients were allergic to Apis venom, 4 to Vespula venom, and 1 to Polistes venom., Results: CD30 serum levels (median, interquartile range) were significantly higher in venom-allergic patients before treatment (33.6 U/mL; 14.8-61.6) than in controls (9.7 U/mL, 1.9-21.3) (P < .000). These levels decreased progressively during treatment in all patients except 2 (P < .000). At the third month of therapy, the levels reached statistical significance in comparison with baseline., Conclusions: This study shows that sCD30 levels are significantly higher in patients with hymenoptera venom allergy and indirectly confirms a preferential T(H)2-type cytokine production in these patients. sCD30 expression decreases during immunotherapy, thus confirming the immunomodulatory role of this treatment in promoting a shift to T(H)1-type cytokines.

Background: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequently reported problem due to the fact that these molecules are often used for control of pain and inflammation. Although the use of selective inhibitors of cyclooxygenase (COX) 2 helps to prevent some of these adverse reactions, they can have cardiac side effects when taken for prolonged periods. Here we report the safety and tolerability of etoricoxib, a selective COX-2 inhibitor with fewer cardiovascular effects, in patients with adverse reactions to NSAIDs., Patients and Methods: We performed placebo-controlled oral challenge with etoricoxib in 65 patients with previous adverse reactions to NSAIDs: 13 to salicylates, 18 to arylpropionic acids, 10 to arylacetic acid, 12 to oxicam and derivates, 8 to pyrazolones, and 4 to acetaminophen (paracetamol). The reported symptoms were urticaria or angioedema in 69%, rhinitis in 3%, and 1 case of anaphylactic shock (1.5%). The challenge was done using the placebo on the first day, half dosage of etoricoxib (45 mg) on the second day, and the therapeutic dose of 90 mg on the third day. The challenge was done in the outpatient department of the hospital and the subjects were monitored for a further 4 to 6 hours after challenge., Results: Oral challenge with etoricoxib was well tolerated in 97% of the patients. Only 2 systemic reactions were reported during the challenge test., Conclusion: Etoricoxib can be considered a safe molecule for those patients with previous adverse reactions to NSAIDs.

Venom immunotherapy (IT) is a very effective method for the treatment of Hymenoptera venom allergy. We compared safety, efficacy, and modulation of specific immunologic parameters in 70 patients sensitized to Apis mellifera, treated for > or = 5 years with standardized quality (SQ) aqueous IT, either with a rush (n = 20) or with a cluster (n = 20) induction protocol, or with an SQ depot extract and a cluster induction protocol (n = 30). We made an open, noncontrolled study. Side effects were monitored and the effects of field stings during the maintenance phase of the treatment and after its interruption were recorded. Skin reactivity to Apis was measured by end point dilution and specific serum immunoglobulin E (IgE) were measured by a solid-phase-based assay. The depot IT was better tolerated than aqueous IT with rush induction. This was caused by mainly the lower frequency in the induction phase of systemic side effects (3.4% versus 36.8% [p < 0.0041] on a "per patient" and 0.1% versus 0.9% [p = 0.0092] on a "per dose "basis, respectively). The cluster protocol with the aqueous extract tended to be better tolerated that the rush protocol. About one-half of patients from each group were re-stung during the study and all suffered only minor discomfort. Reduction of skin reactivity and of serum-specific IgE was significant in the three groups (p < 0.02 in all cases). SQ Depot IT to Apis venom allergy administered with a cluster protocol induces less side effects and is equally effective then IT with SQ aqueous extract administered with a rush protocol.

Background & Aims: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival., Methods: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care., Results: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis., Conclusions: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.

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

Background: Tuftsin activity (TA) is reduced in cirrhosis. This contributes to the defective phagocytic activity (PA) of neutrophil granulocytes and is related to the impairment of splenic function. Orthotopic liver transplantation (OLT) cures cirrhosis and might restore TA. This study was aimed at determining if OLT restores TA and PA., Methods: We measured in 9 cirrhotic patients, before and after successful OLT, TA by a bioassay and PA by chemiluminescence in which neutrophils of the patient were tested with both autologous (PA1) and pooled sera from healthy subjects (PA2). Splenic function was assayed by the pitted red cell count., Results: Before OLT, TA was reduced in 7 patients, and PA1 in all the patients. Pitted cell count was elevated in all the patients. After OLT (median 39 months; range 21-49), TA improved in all cases [median: from 8% (5-16%) to 20% (9-22%), p < 0.008], normalizing in 5 out of the 7 patients with low values. PA1 improved in all the patients [from 102 cpm (65-128 cpm) to 235 cpm (78-280 cpm), p < 0.008], normalizing in 5. Pitted red count decreased in 7 patients and normalized in 3 [from 3.3% (2.1-6.0%) to 2.4% (1.4-2.8%), p < 0.021]. Platelet count [from 55 x 10(3) (30-100) to 185 x 10(3) (93-286), p < 0.008] and leucocyte count [from 3.60 x 10(3) (1.81-5.23) to 5.53 x 10(3) (3.31-6.71), p < 0.008] also improved., Conclusions: OLT improves TA and PA of cirrhotic patients. This effect is associated with an improvement of both functional hyposplenism and haematological hypersplenism. The restoration of natural defences against infections may mitigate the adverse effect of immunosuppressive treatment., (Copyright 2005 S. Karger AG, Basel)

Gamma-hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and nonclinical self-administration. The enhancement of dopamine activity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a mu-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 consecutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its interference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment.

Anaphylaxis is a severe, life-threatening allergic reaction, affecting both children and adults. The occurrence of anaphylaxis is not as rare as generally believed (1.21% to 15.04% of the US population). Often the cause of this reaction remain unknown, mainly due to the difficulty in defining the outbreaking causes. Herein, we describe an interesting case of a patient, who developed an anaphylactic reaction after the bite of a pigeon tick. During the last 2 years, in wintertime, the patient often came to the emergency room for general rash and swelling, hypotension and tachycardia preceded by itching and general distress. Notably, the symptoms manifested themselves as night fell. In two particular occasions the patient reached the hospital in a state of shock. After another episode of general swelling, the patient was invited to examine her domestic environment. She brought us some parasites, collected at home, particularly on the bed. A morphological examination by entomologists proved these parasites to belong to Argas reflexus (Arg.r.), one of the 31 species of soft ticks. The presence of specific IgE to a protein secreted by the Arg.r. salivary glands was in favour of immediate-type systemic reaction, as supposed by the clinical history.

Aim of the Study: To evaluate Anti Cyclic citrullinated peptide (anti-CCP) and Rheumatoid Factor (RF) sensitivity and specificity in patients with Rheumatoid Arthritis (RA)., Materials and Methods: Anti-CCP and RAtest for the assessment of RF have been tried out in 35 patients with RA and in a group of 42 patients whose hands were affected by arthralgic/arthritis-like symptoms., Results: Sensitivity of anti-CCP was 71,4% with 95,2% of specificity. RAtest sensitivity was 91,4% with specificity of 31%. Anti-CCP and RAtest both positive showed an overall 71.4% sensitivity and 95.2% specificity; sensitivity was 91.4% and specificity was 31.0%, if at least RAtest or anti-CCP resulted positive, The positive predictive value of the two test performed together was 97.0%, higher than that of anti-CCP (71.4%) and RAtest (88.5%9) alone. The negative predictive value of the two test performed together was 30.9% similar to that of the RAtest performed alone (30.9%). All patients affected by HCV related chronic liver disease were negative for anti-CCP test; 12/14 of them had RAtest positive., Conclusions: Anti-CCP antibody has a diagnostic specificity higher than RF. Anti-CCP and RA tests together prove to have the some specificity as anti-CCP alone and a lower sensitivity. Sensitivity is better when at least either RAtest or anti-CCP results positive. The best positive predictive value is obtained performing both anti-CCP and RAtest. Anti-CCP is a useful laboratory marker to confirm the diagnosis of rheumatoid arthritis; it seems to be very important to differentiate patients with RA from those with HCV related arthritis.

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

Cinoxacin is an oral synthetic antibacterial agent, of the second generation quinolones group, with excellent efficacy in respiratory, intra-abdominal, pelvic, and skin and soft tissue infections. Overall, quinolones are well tolerated drugs, although phototoxicity and photoallergenicity is well demonstrated experimentally. In this report we show you a case of a man who presented a anaphylactic reaction associated with myocardial infarction, after taking a capsule of cinoxacin. We suppose that there is a direct participation of the heart in anaphylactic reactions, because acttivated mast-cells mediators can determine cardiovascular effects. Then performed double-blind placebo controlled challenge test with an alternative drug. We did not observe any adverse immediate or late adverse reaction to this drug.

Alcohol abuse and alcoholism represent a world-wide problem, both from a medical and a social point of view. In the past the therapy for patients affected by alcoholism was based mainly on the psychological approach. In recent years the use of pharmacotherapy together with psychosocial interventions have enhanced the percentage of success in maintaining alcoholic patients in remission. The present review discusses the main drugs experimented both in preclinical and clinical studies. Pharmacotherapy of alcohol dependence seems to be effective in both alcohol-related emergencies and prevention relapse. However, pharmacotherapy should not be considered as the only form of treatment but as an integrated part of a multimodal approach including psychological and social support.

- Methadone, a synthetic opioid agonist, is commonly used for the treatment of heroin dependence. Depending on how alcohol addiction is defined, rates of alcoholism vary among those attending methadone maintenance treatment (MMT) programmes. Most of the current literature has shown that alcohol consumption increases during medium- or long-term MMT. However, up to now, no data have been reported on changes in alcohol intake among a population of heroin addicts with no alcohol-dependence diagnosis after short-term methadone administration. Thus, the aim of our study was to investigate alcohol consumption changes in a population of non-alcoholic heroin addicts during the first 4 weeks of a treatment programme (TP). The TP consisted of either MMT or non-methadone maintenance treatment (N-MMT) with a minimum duration of 1 year. A total of 359 heroin-addicted out-patients [274 males (76.3%)], all of whom met DSM-IV criteria, were enrolled in the study, over a period of 4 months. Out of these 359 patients, 32 subjects (8.9%) dropped out, whereas 327 subjects (91.1%; 249 males) continued the TP [105 (32.1%; 78 males) in the MMT group and 222 (67.9%; 171 males) in the N-MMT group]. A significant reduction in daily alcohol intake was observed in the MMT group, but not in the N-MMT group after the first 4 weeks of the TP. The results of the present study suggest a possible effect of short-term methadone administration in reducing alcohol consumption in a population of non-alcoholic heroin-addicted patients.

Alcohol abuse is a major risk factor for cancer of the upper alimentary tract, the upper respiratory tract, and liver. Chromosome damage is used as early effect biomarker in the surveillance of human exposure to genotoxic carcinogens. In the present study, two genetic markers, namely chromosome aberrations (CAs) and micronuclei (MN), were used to evaluate genetic damage in peripheral lymphocytes from 20 alcoholics, 20 abstinent alcoholics, and 20 controls. Composition of the three groups was fairly similar as regards sex, age and smoking habits. A highly significant increase was observed in the frequencies of CA and MN in lymphocytes of alcoholics as compared both with controls and abstinent alcoholics. However, no correlation was found between the length of alcohol abuse and the frequencies of either biomarkers in alcoholics. CA and MN frequencies in abstinent alcoholics were similar than those in controls. Our data indicate that CA and MN can be two useful biomarkers to assess genetic damage associated with alcohol abuse. They could be included in programs for cancer prevention in alcoholics. Abstinence appears to normalize the frequency of both MN and CA. This could offer therapists another tool to help alcoholics change their lifestyle.

Venom immunotherapy (VIT) with aqueous extracts is considered a life-saving treatment in insect allergy, but systemic side effects are quite common, especially in patients sensitized to Apis mellifera venom. Only a few studies are available regarding depot VIT administered according to the standard weekly schedule, while no data are available for cluster VIT with depot preparations. This study was designed to compare the tolerance of aqueous cluster or rush VIT versus cluster depot VIT in patients sensitized to Apis mellifera. Fifty-five patients with a history of systemic reaction (grade II to IV according to Müller) after an Apis mellifera sting were divided at random into 3 groups. Forty patients were treated with aqueous VIT (20 according to a cluster schedule and 20 according to a rush schedule) and 15 with Depot VIT according to a cluster schedule. All local and systemic side effects were recorded. Four patients belonging to the aqueous-cluster, 4 belonging to the aqueous-rush, and 1 belonging to the depot-cluster schedule had large local reactions after VIT (p < 0.009). Systemic side effects were recorded in 1, 7 and 0 patients (p < 0.003) respectively. No statistically significant difference was found between the two cluster regimens in the frequency of side effects. Depot VIT administered according to a cluster schedule was well tolerated, and its tolerance is better than aqueous-rush VIT for Apis mellifera.

Alcohol abuse greatly increases the risk of various malignancies, including cancer of the liver and digestive tract. Although it is thought that this may be due, at least partially, to the mutagenic properties of ethanol, little is known about the genotoxic effects of ethanol in humans. We investigated the chromosomal damage in lymphocytes from 20 alcoholics and 20 controls using the micronucleus (MN) assay combined with fluorescence in situ hybridization (FISH) with a pancentromeric DNA probe capable of differentiating centromere positive (C+) from centromere negative (C-) MN. The frequency of MN in binucleate lymphocytes was significantly higher in alcoholics than in controls (12.0 +/- 5.4 and 7.6 +/- 1.6, respectively; P: < 0.05). FISH revealed significantly higher frequencies of C+ MN in alcoholics than in controls (8.2 +/- 4.8 and 3.4 +/- 1.4, respectively; P: < 0.05). In the alcoholics, no association was found between years of alcohol abuse and frequency of MN or C+ MN. However, age influenced MN and C+ MN frequency both in alcoholics and controls. These results indicate that alcohol abuse may well induce chromosome loss in humans, suggesting a possible aneugenic mechanism of alcohol. This effect could contribute to the health hazards related to alcoholism such as cancer risk.

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5; P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th(2)cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections., (Copyright 2000 Academic Press.)

The main objective in alcoholism therapy is to achieve and maintain abstinence and to prevent relapse. Pharmacotherapy may be necessary in treating persons who are not helped by group or psychosocial support alone. Among the substances experimented with in the past few years, gamma-hydroxybutyric acid has been effective in preventing alcohol withdrawal syndrome and in inducing a reduction in craving and an increase in the abstinence rate in treated alcoholics, in view of the alcohol-mimicking effects of the drug on the central nervous system. However, a possible development of craving for the drug and the risk of abuse and physical dependence have been reported in subjects who used gamma-hydroxybutyric acid for different reasons, including alcoholism therapy. The present review updates the existing differences in drug abuse behavior, side effects, and poisoning in the use of gamma-hydroxybutyric acid in a treatment alcoholism program and in self nonclinical illicit use.

The association between venous thromboembolism and cancer has been widely documented and the main factor responsible for cancer-induced venous thromboembolism is considered mostly linked to a hypercoagulation state induced by the cancer itself. There is no consensus on investigative strategies for occult cancer in a patient with a thrombophilic condition. We report a patient who manifested an isolated episode of pulmonary embolism without specific evident sources of venous thromboembolism. The routine clinical and laboratory work-up to detect an occult cancer did not reveal any malignancy. A history of duodenal ulcer in association with a recent slight alteration in bowel habits led us to perform an esophagogastroduodenoscopy which was negative for malignancy, and a barium enema followed by colonoscopy, which revealed the presence of a tumor limited to the large intestine. An unexplained clinically evident hypercoagulation state, even in the presence of mild clinical symptoms, needs more thorough diagnostic strategies when simple methods of screening for occult cancer are negative.