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• We report a case of cerebral amyloid angiopathy presenting as a fronto-temporal dementia.

Changes in rhinitis symptom severity tend to decrease with aging, but whether the decrease is associated with allergic skin test reactivity, serum total and specific IgE, and nasal eosinophils or determined only by aging is poorly understood. The aim of the study was to analyze sensitivity in vivo and in vitro some 15 years after primary testing, skin prick test (SPT), serum total and specific IgE, ratio sIgE/tIgE, and nasal eosinophils in order to evaluate changes due to age and changes due to the severity of rhinitis symptoms. One hundred and eight rhinitis patients who had been investigated in 1995 were re-interviewed and their current allergy re-assessed after a follow-up of 15 years. All patients were SPT with eight common allergens in the area of Palermo (Italy). Rhinitis symptoms tended, on average, to have become milder at the follow-up. All parameters examined showed a decreasing trend in older age groups over the period between the two investigations. Rhinitis symptoms tend to become milder and the allergic parameters both in vivo and in vitro usually decrease in the long run; however, the changes in rhinitis symptoms appear to be related to changes in the nasal eosinophils, independently of SPT and serum-specific IgE.

Osteoporosis and osteomalacia are, to date, among the most common metabolic diseases in the world. Lately, an association between metabolic bone diseases and chronic liver disease has been increasingly reported, inducing many authors to create a new nosographic entity known as 'hepatic osteodystrophy.' The importance of such a condition is further increased by the morbidity of these two diseases, which greatly reduce the quality of life because of frequent fractures, especially vertebral and femoral neck ones. For this reason, early identification of high-risk patients should be routinely performed by measuring bone mass density. The explanation for the association between bone diseases and chronic liver disease is still uncertain, and involves many factors: from hypogonadism to use of corticosteroid drugs, from genetic factors to interferon therapy. To date, few studies have been conducted, and all with a small number of patients to establish definitive conclusions about the possible treatment, but some evidence is beginning to emerge about the safety and efficacy of bisphosphonates.

Type 2 diabetes is associated with a cluster of inter-related plasma lipid and lipoprotein abnormalities, including reduced HDL-C, a predominance of small, dense LDL and elevated triglycerides. These abnormalities occur even in prediabetes, before blood sugars rise sufficiently in order to confirm a diagnosis of diabetes, and this transition phase incurs important cardiovascular risk. This is the rationale for paying attention to dyslipidemia through the use of the hypolipidemic, rather than hypoglycemic drugs only. A literature search (by Medline and Scopus) was performed. The authors also manually reviewed the references of selected articles for any pertinent material. Beyond the ‘quantity’ of LDL, several lipid-lowering agents and particularly statins, are only in part beneficial on the ‘quality’ of LDL, so that their net effect on small, dense LDL is moderate. Among hypoglycemic agents, insulin and metformin have shown a limited role on small, dense LDL, while pioglitazone is more beneficial. The effi...

Cortico-basal syndrome (CBS) is a rare neurodegenerative disease characterised by movement and cognitive disorders. It occurs along the spectrum of fronto-temporal lobar degeneration (FTLD), which also includes fronto-temporal dementia (FTD) and progressive supranuclear palsy (PSP). FTLD has recently been shown to be associated with mutations in GRN gene, coding for progranulin, a multifunctional secreted glycoprotein involved in cell cycle, inflammation and tissue repair. We describe the case of a 73-year-old man suffering from CBS with a family history of cognitive disorders belonging to the clinical spectrum of FTLD. Sequencing analysis of GRN in this patient revealed that the C157KfsX97 null mutation has been already described by Le Ber et al. in a French patient affected by an apparently sporadic form of FTD. This report confirms the variability of clinical phenotypes associated with the same mutation and emphasises the importance of genetic analysis in cases with a clear familiarity, as well as in apparently sporadic forms.

BACKGROUND & AIMS: A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. METHODS: Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. RESULTS: Twenty-four of the patients (20%) had FH (cow's milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. CONCLUSIONS: A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms.

Background and aims Growing evidence suggests that the metabolic syndrome (MetS) has both a genetic and environmental basis. To evaluate the possibility of a further genetic analysis, we estimated prevalence rates and heritabilities for the MetS and its individual traits in the adult population of Linosa, a small and isolated Italian Island in the southern-central part of the Mediterranean Sea. Methods and results The Linosa Study (LiS) group consisted of 293 Caucasian native subjects from 51 families (123 parents; 170 offsprings). The MetS was defined according to NCEP/ATP III criteria and the following prevalence rates were calculated: hyperglycaemia 20.3%; central obesity 34.9%; hypertension 43.4%; hypertriglyceridaemia 29.9%; "low HDL" 56.6%; MetS 29.9%. Waist circumference was significantly related to all the quantitative parameters included in the NCEP/ATP III MetS definition. The MetS showed a heritability of 27% ( p =0.0012) and among its individual components, treated as continuous and discrete traits, heritability ranged from 10% for blood glucose to 54% for HDL-cholesterol. Among MetS subtypes, the clustering of central obesity, hypertriglyceridaemia and "Iow HDL" had the highest heritability (31%; p Conclusion These data showed high prevalence rates for the MetS and its related traits in an isolated and small Caucasian population. The appreciable heritability estimates for the MetS and some of its components/clusters in the LiS population might support the observation of genetic factors underlying the pathogenesis of the MetS and encourage further analysis to identify new susceptibility genes.

SummaryBackgroundEpidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD).MethodsWe studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum.ResultsThe age was not different in patients with COPD (n=28) and asthma (n=21) (70.2±3.9 years vs. 69.6±3.7 years), also the degree of fixed airflow obstruction was similar (FEV1: 58.3±1.5% vs. 59.0±1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43±0.05×10−3μL vs. 0.27±0.1×10−3μL, P

Alzheimer disease (AD) is the most prevalent form of dementia. Loss of hippocampal synapses is the first neurodegenerative event in AD. Synaptic loss has been associated with the accumulation in the brain parenchyma of soluble oligomeric forms of amyloid β peptide (Aβ1-42wt). Clinical observations have shown that a mutation in the APP protein (A673V) causes an early onset AD-type dementia in homozygous carriers while heterozygous carriers are unaffected. This mutation leads to the formation of mutated Aβ peptides (Aβ1-42A2V) in homozygous patients, while in heterozygous subjects both Aβ1-42wt and Aβ1-42A2V are present. To better understand the impact of the A673V mutation in AD, we analyzed the synaptotoxic effect of oligomers formed by aggregation of different Aβ peptides (Aβ1-42wt or Aβ1-42A2V) and the combination of the two Aβ1-42MIX (Aβ1-42wt and Aβ1-42A2V) in an in vitro model of synaptic injury. We showed that Aβ1-42A2V oligomers are more toxic than Aβ1-42wt oligomers in hippocampal neurons, confirming the results previously obtained in cell lines. Furthermore, we reported that oligomers obtained by the combination of both wild type and mutated peptides (Aβ1-42MIX) did not exert synaptic toxicity. We concluded that the combination of Aβ1-42wt and Aβ1-42A2V peptides hinders the toxicity of Aβ1-42A2V and counteracts the manifestation of synaptopathy in vitro. Finally we took advantage of this finding to generate a cell-permeable peptide for clinical application, by fusing the first six residues of the Aβ1-42A2V to the TAT cargo sequence (Aβ1-6A2VTAT(D)). Noteworthy, the treatment with Aβ1-6A2VTAT(D) confers neuroprotection against both in vitro and in vivo synaptopathy models. Therefore Aβ1-6A2VTAT(D) may represent an innovative therapeutic tool to prevent synaptic degeneration in AD.

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (

Adult thalassemic patients have reduced bone mass due to disturbances in several different mechanisms affecting bone turnover. To determine if vitamin D deficiency contributes to the low bone mass of adult thalassemic subjects, we studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and 48 years) affected with thalassemia major (TM) and 35 (age 21-56 years) with thalassemia intermedia (TI). TM patients had been receiving regular transfusions from the age of 2 years and had increased serum ferritin, glutamic oxalacetic transaminase, glutamic piruvic transaminase as well as low bone density (L1-L4 Z score -2.07 +/- 0.2). TI patients did not receive transfusions, but their ferritin levels were increased as well (520.3 +/- 138,1). 8 TM patients (10.1%) and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D was significantly (P < 0.01) lower in both TM and TI patients (20.3 +/- 0.7 ng/ml and 20.9 +/- 2.3 ng/ml, respectively) than in 100 healthy control subjects of similar age (25.2 +/- 1 ng/ml). 1,25-OH-vitamin D levels were in the normal-lower levels (45.15 +/- 1.5 mg/dl), while 24 H urinary calcium was below the normal range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI patients with low 25-OH-vitamin D levels (

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P

The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes which codify for the metabolism enzymes, receptor proteins, or protein targets of chemotherapy agents often present various genetic polymorphisms. The main aim of this review is to provide an overview of the known polymorphisms present in the genes which codify for factors (thymidylate synthase dihydropyrimidine dehydrogenase, uridine diphosphate (UDP)-glucuronosyl-transferase 1A1, enzymes implicated in DNA repair) involved in the action mechanisms of the drugs now utilized in chemotherapeutic treatment of colorectal carcinoma, such as fluoropyrimidines, irinotecan, and platinum agents.

Background: Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying “organic” causes of chronic diarrhea in consecutive adults and children.Methods: We consecutively enrolled 70 adult patients (30 males, 40 females; median age, 35 years) and 50 children (20 males, 30 females; median age, 3.5 years) with chronic diarrhea of unknown origin. All patients underwent a complete work-up to identify the causes of chronic diarrhea. FC was measured by ELISA.Results: In adult patients, FC showed 64% sensitivity and 80% specificity with 70% positive and 74% negative predictive values for organic causes. False-positive results (8 of 40 cases) were associated with the use of aspirin (3 cases) or nonsteroidal antiinflammatory drugs (1 case) and with the presence of concomitant liver cirrhosis (3 cases). False-negative results mainly included patients suffering from celiac disease (5 cases). Patients with IBD (9 cases) were identified with 100% sensitivity and 95% specificity. In pediatric patients, sensitivity was 70%, specificity was 93%, and positive and negative predictive values were 96% and 56%. False-negative results (11 of 35 cases) were associated mainly with celiac disease (6 cases) or intestinal giardiasis (2 cases).Conclusions: FC assay is an accurate marker of IBD in both children and adult patients. In adults, false negatives occur (e.g., in celiac disease) and false-positive results are seen in cirrhosis or users of nonsteroidal antiinflammatory drugs. Diagnostic accuracy is higher in children.

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

Background & Aims Rectal bleeding and lymphonodular hyperplasia (LNH) in children can be caused by food hypersensitivity (FH). Our aim was to verify whether similar clinical and endoscopy presentations in adults can be due to FH. Methods Consecutive adult patients with rectal bleeding were enrolled. All underwent routine assays, colonoscopy, and histology study. Results Ten of 64 (15%) patients showed LNH as the unique sign at colonoscopy. An oligoantigenic diet resolved the rectal bleeding in 9 patients, and the reintroduction of several foods caused symptom reappearance. Double-blind placebo-controlled challenges with cow's milk and wheat protein confirmed the FH; symptoms reappeared 1–96 hours after the challenge. None of the patients were positive for IgE-mediated assays. In patients with LNH and FH, histology of the ileum and colon mucosa showed a higher number of lymphoid follicles and intraepithelial and lamina propria eosinophils compared with the other patients with rectal bleeding. Conclusions Recurrent rectal bleeding can be caused by FH in adult patients. Endoscopic evidence of LNH characterizes these cases.

The gastrointestinal tract of healthy individuals is colonized by hundreds of saprophytes and mycetes, especially the Candida species, are habitual ones. Under certain conditions, the fungal flora may overgrow, resulting in lesions of the digestive mucosa which, rarely, can have a local diffusion and/or spread to the lympho-hematogenous system. Mycotic infections of the stomach can sometimes look like benign gastric ulcers. Here, we present the case report of a woman, aged 64, who presented with type II diabetes mellitus and psoriasis, on chronic treatment with cyclosporin A and with endoscopic evidence of an ulcerated, vegetating gastric lesion secondary to Candida albicans infection. Although strongly suggestive of malignancy, it completely healed after cyclosporin withdrawal and the administration of oral antifungal drugs.

The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum. Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.

Background Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. Aim To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. Patients and methods The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. Results EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. Conclusion EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in 'seronegative' patients. Eur J Gastroenterol Hepatol 23:1018-1023 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies were initially developed in order to avoid the cytotoxic effects of chemotherapy on healthy tissues. However antibodies have not yet replaced chemotherapy agents, since the combination of both kinds of drugs have usually appeared to achieve higher benefit compared with chemotherapy alone. The research for the development of new monoclonal antibodies aims to identify further targets and to provide innovative antibody constructs.

Background Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity. Aims We evaluated the bread wheat line C173 for its effects on the in vitro -grown duodenal mucosa of CD patients. Methods In vitro -grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadin–glutenin subunits, analyzed for morphology, cytokine and anti-tTG antibody production, and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore. Results Duodenal mucosa biopsies exposed to prolamins from C173 and San Pastore released higher amounts of IFN-γ, IL-2, IL-10 and anti-tTG antibodies in the culture medium than untreated controls. The line C173 differed from cv. San Pastore as it did not produce negative effects on enterocyte height, suggesting that manipulating prolamin composition can affect innate immune responses of CD mucosa to wheat gluten. Conclusions Our data demonstrated that this gliadin-deficient wheat has a lower direct toxicity but activates an immunologic reaction of the duodenal mucosa like that of the common wheat species.

Background & Aims Some patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH); their symptoms improve when they are placed on elimination diets. No assays identify patients with FH with satisfactory levels of sensitivity. We determined the frequency of FH among patients with symptoms of IBS and the ability of fecal assays for tryptase, eosinophil cationic protein (ECP), or calprotectin to diagnose FH. Methods The study included 160 patients with IBS, 40 patients with other gastrointestinal diseases, and 50 healthy individuals (controls). At the start of the study, patients completed a symptom severity questionnaire, fecal samples were assayed, and levels of specific immunoglobulin E were measured. Patients were observed for 4 weeks, placed on an elimination diet (without cow's milk and derivatives, wheat, egg, tomato, and chocolate) for 4 weeks, and kept a diet diary. Those who reported improvements after the elimination diet period were then diagnosed with FH, based on the results of a double-blind, placebo-controlled, oral food challenge (with cow's milk proteins and then with wheat proteins). Results Forty of the patients with IBS (25%) were found to have FH. Levels of fecal ECP and tryptase were significantly higher among patients with IBS and FH than those without FH. The ECP assay was the most accurate assay for diagnosis of FH, showing 65% sensitivity and 91% specificity. Conclusions Twenty-five percent of patients with IBS have FH. These patients had increased levels of fecal ECP and tryptase, indicating that they might cause inflammation in patients with IBS. Fecal assays for ECP could be used to identify FH in patients with IBS.

Objective To report the clinical, genetic, neuroimaging, and neuropathologic studies of patients with the hereditary cerebral hemorrhage with amyloidosis linked to the APP E693K mutation. Design Case series. Clinical details and laboratory results were collected by direct evaluation and previous medical records. DNA analysis was carried out in several affected subjects and healthy individuals. Neuropathologic examination was performed in 2 subjects. Setting Southern Lombardy, Italy. Patients Individuals with and without amyloidosis in 4 unrelated Italian families (N = 37). Main Outcome Measure Genotype-phenotype relationship. Results The affected individuals presented with recurrent headache and multiple strokes, followed by epilepsy and cognitive decline in most of them. The disease was inherited with an autosomal dominant trait and segregated with the APP E693K mutation. Neuroimaging demonstrated small to large hematomas, subarachnoid bleeding, scars with hemosiderin deposits, small infarcts, and leukoaraiosis. Amyloid-β immunoreactivity was detected in the wall of leptomeningeal and parenchymal vessels and in the neuropil, whereas phosphorylated tau, neurofibrillary changes, and neuritic plaques were absent. Conclusions These findings expand the number of APP mutations linked to hereditary cerebral hemorrhage with amyloidosis, reinforcing the link between this phenotype and codon 693 of APP .

No two customers are identical, even whereas they belong to the same marketing program or they choose the same product or service (Withiam G., 2000). Revenues, costs and therefore profitability differ because of the different effort required to meet the specific need of the specific consumer or group of customers. When competing, firms target information towards specific segments through direct marketing initiatives and actions (Cross R.G., 1997). This finding underlines the importance of knowing in advance customer’s characteristics, even before thinking at the service to provide, and aims to illustrate how the lodging industry normally segments its customers, and which group of customers we may retrieve within the industry. The framework of this article involves four main topics, which cover the theories behind the strategies, the actual configuration of the market segmentation within the lodging industry, the hotel response in terms of product differentiation with a hint on the crucial decision between standardization and customization, and ending with the strategies behind results. The purpose of the finding relies on the statement that two customers are not even similar and in this sense, hotels should invest on studies aimed at understanding the consumer’s behavior (Dall’Ara G., 2009). Choosing the right approach at the right time for the right consumer would stand at increasing the retention, building relationships and customize a one-to-one marketing approach. On an economic point of view, targeting customers would also lead firms to the implementation of the customer profitability analysis, which allow hotels to assign activities and thus costs, revenues and profits (Fasone V., 2007). In this paper, this will be demonstrated not only through the international literature and the hotel newsletters on the topic, but also through a direct study on a four stars’ property, through which the reader will distinguish between the two different approaches, i.e. fitting strategies on customer’s shoes rather than applying the same business strategy.

Background Recurrent aphthosis is a common oral ulcerative condition consisting also of a subset of similar ulcers, properly named 'aphthous-like' ulcers (ALU), linked to systemic diseases and among these, to iron, folic acid and vitamin B(12) deficiencies. Objectives The main objectives of this study were: (i) to evaluate the association between recurrent aphthosis and the most common predisposing factors; (ii) to assess the frequency of ALU in recurrent aphthosis; (iii) to verify the efficacy of a replacement therapy in all ALU patients. Methods Thirty-two adults with recurrent aphthosis and 29 otherwise healthy controls were consecutively recruited, interviewed and subjected to haematological investigations. Results Family history of recurrent aphthosis was significantly associated (P < 0.01). The overall frequency of haematinic deficiencies was 56.2% in recurrent aphthosis patients vs. 7% in controls (P < 0.0001). All ALU patients with a negative family history showed a complete remission of the ulcerative episodes after replacement therapy, while those with a positive family history only had a reduction in frequency and severity. In the logistic regression model, only family history was associated with recurrent aphthosis (P = 0.0137). Conclusion The strong association with familiarity, the unexpected higher frequency of ALU (compared with the idiopathic variant) and the good response to replacement therapy means that familiarity should always be investigated. Furthermore, routine haematological screening and tests for serum iron, folic acid and vitamin B(12) deficiencies should be assessed in all patients with recurrent aphthosis to treat any nutritional deficiency and to prevent more important related systemic manifestations.

During uncertain times a deeper attention on strategies is highly recommended in order to minimize the loss and maintain, or gain in certain cases, market share (Vergara C., 2004). In this direction, hotels are asked to invest more in Revenue Management intelligence, not only toward the actual practices based on Room Revenue, but also taking into consideration the other incoming departments and in particular Food & Beverage. This article aims to clearing up the current state of the Revenue Management theory and practice, starting from its origin, crossing the five pillars, or the current policies and ending with a brief hint on the future of the entire hotel industry, which here we may call as Total Revenue Management or Revenue Management 100% thereof.

OBJECTIVE: Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined. DESIGN: We measured concentrations of apoB, Lp(a) and small, dense low-density lipoprotein (LDL) in 42 patients with PCOS [age: 28 +/- 7 years, body mass index (BMI): 27 +/- 5 kg/m(2)] vs. 37 age- and BMI-matched healthy controls. METHODS: Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l. RESULTS: Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.0131) while total- and LDL cholesterol were similar. PCOS also showed smaller LDL size (p = 0.0005), higher levels of total small, dense LDL (p < 0.0001), higher concentrations of Lp(a), as considered as absolute values (p = 0.0143) and log-transformed (p = 0.0014), while no differences were found in apoB levels. Elevated Lp(a) concentrations were found in 24% of PCOS, while elevated apoB levels were relatively uncommon (14%). Spearman correlation analysis revealed that Lp(a) concentrations were weakly correlated only with HDL-cholesterol levels (r = -0.378, p = 0.0431). In addition, 36% of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a), apoB or small, dense LDL. CONCLUSIONS: Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern. Future prospective studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS.

BACKGROUND: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease. METHODS: Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin. RESULTS: Intra-epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002). CONCLUSIONS: Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.

Clinical presentation of Crohn’s disease (CD) may be variable according to the location and the intensity of the inflammation. Some patients may have atypical symptoms which could delay the diagnosis. We report the first case of chronic urticaria related to a subclinical, complicated CD. Although the pathologic mechanism of this association was unclear in our patient, this case suggests that in patients with unexplained chronic urticaria it is opportune to investigate for a possible CD, even if there are no or few specific symptoms of intestinal inflammatory disease.

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the extrinsic/intrinsic pathway, proteins that control the apoptosis machinery such as the p53 and proteosome pathway. Most of these forms of therapy are still in preclinical development because of their low specifity and susceptibility to drug resistance, but several of them have shown promising results. In particular, this review specifically aims at providing an update of certain molecular players that are already in use in order to target apoptosis (such as bortezomib) or which are still being clinically evaluated (such ONYX-015, survivin and exisulind/aptosyn) or which, following preclinical studies, might have the necessary requirements for becoming part of the anticancer drug programs (such as TRAIL/ Apo2L, apoptin/VP3). Key words: apoptosis, TRAIL/Apo2L, apoptin/VP3, ONYX015, Bortezomib, exisulind, survivin

OBJECTIVE: To evaluate the role of social and cultural differences inside the same ethnic group on the ovulatory status of women with polycystic ovary syndrome (PCOS). DESIGN: To correlate social and cultural status with the phenotypic expression (body weight and ovulation) and with androgen and insulin levels of PCOS. SETTING: University department of medicine. PATIENT(S): Two hundred and forty-four consecutive PCOS women. INTERVENTION(S): All studied patients completed a simple questionnaire to indicate their mean family income and their school education. MAIN OUTCOME MEASURE(S): Ovulation was assessed by measurement of serum progesterone on day 22 of a spontaneous or induced menstrual cycle. Levels of blood testosterone, sex hormone-binding globulin, insulin, and blood glucose were evaluated. RESULT(S): In the low to medium income group, 21% of patients had ovulatory PCOS, but the prevalence of the same PCOS phenotype was 43% in patients with high income. In patients with low education, only 12% presented with ovulatory PCOS compared with 47% of the patients with high education status. Mean family income negatively correlated with body mass index, waist circumference, insulin, and insulin resistance. Serum progesterone correlated negatively with insulin and insulin resistance. CONCLUSION(S): In an ethnically homogeneous PCOS population, high socioeconomic status was associated with a higher prevalence of the ovulatory phenotype. Differences in ovulatory status between the social classes seem to be related to differences in insulin levels and fat quantity and distribution.

Objective To verify the conclusions of the Endocrine Society Guidelines that patients with mild hirsutism and no other important clinical signs (menstrual irregularities, infertility, central obesity, acanthosis nigricans, rapid progression of the hirsutism, clitoromegaly) should not be further studied. Design Retrospective study in patients referred because of mild hirsutism and no other clinical signs. Setting Department of Clinical Medicine of the University of Palermo. Patient(s) One hundred fifty-two patients with mild hirsutism. Intervention(s) Measurement of serum testosterone, dehydroepiandrosterone sulfate, 17-OH-Progesterone, assessment of ovulation by measurement of progesterone in 21 to 24 days and ovarian ultrasound. Result(s) In 72 (47%) patients a diagnosis of polycyctic ovarian syndrome (PCOS) was performed. Polycyctic ovarian syndrome patients included 56 patients with the mild ovulatory form (OV-PCOS) but also 16 patients with the anovulatory form (classic PCOS). Three (2%) patients had nonclassic adrenal hyperplasia. Conclusion(s) Because of the high prevalence of PCOS and the possibility of finding nonclassic 21-hydroxylase deficiency, patients with mild hirsutism need a diagnostic evaluation that should include 17-hydroxyprogesterone measurement plus assessment of ovulation and ovarian ultrasound.

Polymorphisms of the CYP450 genes that encode for the enzymes that metabolize estrogen are linked to hormone-related cancers. We investigated the impact of two polymorphisms of the CYP1B1 gene previously reported to be associated with hormone-related disorders on estrogen metabolism and bone mineral density (BMD), another hormone-dependent condition, in women from different ethnic backgrounds. Four hundred sixty-eight postmenopausal Caucasian women, 220 from St. Louis, MO, USA (mean age=63.5±0.53 years) and 248 from Palermo, Italy (mean age=72.9±0.44 years) participated in the study. Measurements of urinary estrogen metabolites by enzyme-linked immunoassay, serum estradiol by ultrasensitive radioimmnunoassay, and serum sex hormone-binding globulin by immunoradiometric assay were performed only in the American women, while BMD by dual energy X-ray absorptiometry and genotyping by pyrosequencing were performed in both American and Italian women. Differences in the levels of metabolites, free estradiol index and BMD were analyzed by analysis of covariance. Analysis among the American participants for the Valine432Leucine polymorphism showed that, compared to women with the Val/Val genotype, women with the Leu allele (Val/Leu and Leu/Leu) had significantly higher log-transformed values of total urinary estrogen metabolite (ng/mg-creatinine) levels (1.23±0.04, 1.35±0.02, and 1.34±0.03; p=0.03), and significantly lower BMD (gm/cm2) in the lumbar spine (1.009±0.02, 0.955±0.01 and 0.931±0.02; p=0.03) and the femoral neck (0.748± 0.02, 0.717±0.01 and 0.693±001, p =0.03) for the Val/Val, Val/Leu and Leu/Leu genotypes respectively. There were no significant differences in the urinary metabolites and BMD in the different genotypes for the Alanine119Serine polymorphism among the American women. Meanwhile, a separate analysis among the Italian women revealed no significant differences in BMD among the different genotypes for the two polymorphisms investigated. In conclusion, women with the Leu allele for the CYP1B1 Val432polymorphism have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites, compared to those with Val/Val genotype. This may lead to relative hypoestrogenism and lower BMD in the lumbar spine and femoral neck in these women. Our data suggest that through its effect on the rate of estrogen catabolism, the Val432Leu polymorphism of the CYP1B1 gene may represent as a possible genetic risk factor for osteoporosis in American women.

Creutzfeldt-Jakob disease (CJD) is typically characterized by rapidly progressive dementia and myoclonus, and it is caused by a conformational change of the prion protein. The heritable forms are associated with mutation in the gene encoding the prion protein (PRNP). We report a 63-year-old Italian woman harboring the E200K PRNP mutation. Electroencephalogram, cerebrospinal fluid analysis, PRNP gene sequencing, histopathologic examination, immunohistochemical studies, and Western blotting analysis confirmed the diagnosis of CJD. Pyramidal involvement was the first sign and the prominent clinical feature. Later on, she developed also myoclonus, ataxia, spastic tetraplegia, and at last dementia with akinetic mutism. Usually, signs of degeneration of the pyramidal tracts occur in a small number of patients as the disease advances. Our report supports the variability of the clinical expression of the E200K genetic CJD. Further studies are needed to understand the molecular basis underlying the phenotypic variability among patients carrying this mutation.

BACKGROUND: Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) but its prevalence in different PCOS phenotypes is still largely unknown. METHODS: We measured plasma lipids and lipoproteins in 35 anovulatory PCOS (age: 25 ± 6 years, BMI: 28 ± 6 kg/m2), 15 ovulatory PCOS (age: 30 ± 6 years, BMI: 25 ± 3 kg/m2) and 27 healthy women (controls) age- and BMI-matched with ovulatory PCOS. PCOS was diagnosed by the presence of clinical or biologic hyperandrogenism associated with chronic anovulation and/or polycystic ovaries at ultrasound. In women with normal menses chronic anovulation was indicated by low serum progesterone levels (

Background Recent findings have suggested that subjects with non-coronary atherosclerosis may show elevated prevalence of atherogenic dyslipidemia, including higher triglyceride levels, reduced HDL-cholesterol concentrations and increased levels of small, dense low-density lipoproteins (LDL). These three lipid abnormalities constitute the so-called “atherogenic-lipoprotein-phenotype” (ALP) but its predictive role in these patients still remains to be established. Methods We performed a 2-year follow-up study to assess clinical and biochemical predictors of cardiovascular events in 44 male patients (64 ± 5 years, BMI: 27 ± 3), 26 with peripheral arterial disease and 18 with abdominal aortic aneurysm. Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Results Clinical events were registered in the 43% of patients. At univariate analysis we found that patients with events had increased prevalence of hypertension (p = .0098), diabetes (p = .0089), family history of cardiovascular diseases (p = .0089), of elevated small, dense LDL (p = .0222) and ALP (p = .0224). At multivariate analysis (including all clinical and laboratory variables) we found the following independent predictors of events: hypertension (OR 8.9, p = .0347), diabetes (OR 9.4, p = .0270), elevated small, dense LDL (OR 6.9, p = .0488) and ALP (OR 8.7, p = .0497). Conclusions This is the first study that evaluated the predictive role of ALP beyond traditional cardiovascular risk factors in patients with peripheral arterial disease or abdominal aortic aneurysm. We confirmed that hypertension and diabetes are strong predictors of cardiovascular events in these subjects but ALP seems to be an independent predictor too. Yet, the therapeutical consequences of these findings need to be tested by future studies.

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common allele. None of the non-carriers of the mutation or of the 50 healthy Sicilian controls showed this haplotype. This allelotype analysis highlighted the presence of a common allele (ancestor), thus suggesting the presence of a founder effect in the Sicilian population. Our results are in contrast with other studies but only the allelotype analysis of all the BRCA1-5083del19 mutation carriers of two neighboring regions of the south of Italy (Calabria and Sicily) will make it possible to identify the real ancestor of this mutation.

OBJECTIVE: Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and "atypical" gastrointestinal symptoms in CD patients on a GFD. MATERIAL AND METHODS: Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17-62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24-71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal histologic study. RESULTS: Persistent endoscopic lesions were more frequent in Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was significantly more frequent in Group A than in Group B: 85% versus 33% (p

Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It is mostly expressed in neuronal and glial cells but it is also present in non-neural cells such as fibroblasts and lymphocytes. An altered tau produces cytoskeleton pathology resulting in neurodegenerative diseases such as Alzheimer's disease and tauopathies. Tau has been suggested to be a multifunctional protein, due to its localization in different cellular compartments. However its further functions are still unclear. We analyzed the distribution of tau in human skin fibroblasts showing its localization in the nucleus and along mitotic chromosomes. Then, we investigated if an altered tau, such as the P301L mutated protein associated with frontotemporal dementia, could produce nuclear pathology. We found that patients carrying the mutation consistently had several chromosome aberrations in their fibroblasts and lymphocytes: chromosome and chromatid breakages or gaps, aneuploidies, translocations, in addition to chromatin bridges and decondensed chromosomes. Our findings argue for a role of tau in chromosome stability by means of its interaction with both microtubules and chromatin.