Electrochemical Deposition of Polypyrrole in the Presence of Silanes as Adhesion Promoters.

Polypyrrole adhesion to indium-tin oxide electrodes was improved by adding pre-hydrolyzed alkoxysilanes to the electrodeposition media. The pyrrole oxidation and film growth rates were studied by potentiostatic polymerization in acidic media. The morphology and thickness of the films were studied by contact profilometry and surface-scanning electron microscopy. The bulk and surface semiquantitative chemical composition was studied by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Finally, the adhesion was studied by scotch-tape adhesion test, where both alkoxysilanes showed a significant improvement in adhesion. We proposed a hypothesis for the improvement in adhesion, that involves the formation of siloxane material as well as in situ surface modification of the transparent metal oxide electrode.

Modalities for assessing the nutritional status in patients with diabetes and cancer.

Epidemiological data have shown that an increased body mass index (BMI) is associated with a higher risk of various cancers, especially in obese diabetic patients. However, oncologic patients often present nutritional alterations that can worsen their prognosis. The aim of this review is to propose the use of cheaper and easy to use tools to assess the nutritional status of patients with cancer with altered glucose metabolism. Based on a literature review, we propose anthropometric measures to classify the degree of malnutrition. Moreover, the Karnofsky Performance Status (KPS) and the Eastern Cooperative Oncology Group's performance index (ECOG) are useful to assess the functional status of the body; the achievement of nutritional needs can be analysed with the PG-SGA questionnaire, while the quality of life can be investigated using the DTSQ, SF36, EQ-5D questionnaires and the Edmonton Symptom Assessment System. Pre-albumin dosage and lymphocyte count are proposed as nutritional parameters. The degree of hydration can be evaluated through the Bio-Impedance Test (BIA), and energy intake through the dairy food diary, which considers the type of nutrition and the consistency of the meals. It is possible to use a score for each tool used, which is useful to plan an adequate nutritional intervention.

Positron emitting tracers in pre-clinical drug development.

Molecular imaging tools such as Positron Emission Tomography (PET) are increasingly being used in the drug development process. The unrivaled sensitivity of PET coupled with a solid experience in developing highly targeted molecular probes makes this technique a very valuable tool at all stages from pre-clinical development to the clinical phases. Positron emitting tracers allow us to measure, quantitatively, molecular processes and interactions between a candidate drug and its molecular targets. This information can save time and money by directing development towards the most promising compounds and excluding molecules with unfavorable properties that would otherwise only be recognized as failures in latter stages of the process. In this paper we review the application of positron emitting tracers in the pre-clinical stages of the drug development process in the areas of oncology, cardiology, neurosciences and inflammatory diseases. PET tracers provide an important support for drug development in the areas of: discovery of new drug targets, clarification of pathophysiology, identification of potential drug candidates and validation of drug effectiveness, as well as the evaluation of pharmacokinetic and pharmacodynamic parameters in vivo.

Lymphoepithelial cyst of the pancreas: case report and review of the literature.

BACKGROUND AND STUDY AIMS: Lymphoepithelial cyst of the pancreas (LCP) is a rare, benign cyst mimicking pseudocyst or cystic neoplasm. Literature describing LCP is limited to case or brief series reports, and the natural history of this condition is largely unknown. A literature review was carried out in order to elucidate the clinical, pathological and biochemical features of LCP. The aim of this study was to define diagnostic criteria and treatment. METHODS: A Medline and Pubmed search was conducted by using the key-words "lymphoepithelial cyst" and "pancreas". The articles found were accurately examined and all details regarding clinical and pathological features were included in a data-base. Furthermore, a case recently observed in our unit was added to the review. RESULTS: Ninety-two cases of LCP were found in the worldwide literature, including the case that we observed. LCP occurs more frequently in males (M:F=5.5:1), its preferred site is the tail of the pancreas, and its size ranges between 2 and 10centimetres. Histologically, it is a true cyst delineated by a keratinizing squamous epithelium surrounded by lymphoid tissue. LCP is asymptomatic in the majority of cases and preoperative diagnosis is complicated by a lack of specific radiological features of the disease. An accurate preoperative diagnosis can only be made by obtaining cytological specimens and placing them in the hands of a pathologist who is familiar with the cytological appearances of the disease. CONCLUSIONS: LCP is a rare lesion worldwide, without any prevalence in different countries or in different ethnic groups. Understanding the features of LCP, making an accurate diagnosis and differentiating it from cystic neoplasm preoperatively is vital, as when it is diagnosed certainly, a conservative treatment is justified. Otherwise, radical surgery in the form of pancreatic resection is required to exclude the diagnosis of pancreatic cystic neoplasm.

Liver resection for intrahepatic stones in congenital bile duct dilatation.

OBJECTIVE: This study reports our clinical experience with liver resection for congenital dilatation of the intrahepatic bile duct and intrahepatic gallstones to evaluate results and define indications for treatment. PATIENTS AND METHODS: We studied the clinical data of patients who underwent hepatic resection for intrahepatic lithiasis from January 1992 to December 2008 and assessed the immediate and long-term results of these interventions. RESULTS: Of 49 treated patients, 47 underwent liver resection. In the majority of cases, the disease was limited to the left lobe and left hepatectomy was the most commonly performed surgical procedure. The operative mortality was zero with morbidity in 24.5% of patients. Cholangiocarcinoma was diagnosed in six cases (12.2%). In 91.6% of cases the long-term results were good or satisfactory. CONCLUSION: Treatment goals in all cases should be the elimination of intrahepatic stones, the prevention of recurrent lithiasis, and prevention or cure of cholangiocarcinoma. Surgical excision is the best possible treatment for symptomatic patients with localized disease and atrophy of the affected liver.

Gas in portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer.

OBJECTIVES: Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction. METHODS: After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement. RESULTS: Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy. CONCLUSIONS: This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.

Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people.

BACKGROUND AND AIM: The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form. METHODS AND RESULTS: Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p<0.03) and LDL (-4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting. CONCLUSIONS: Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection.

Orthotopic liver transplantation (OLT) is a successful therapy for patients with end-stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow-up, 27 patients had at least 1 episode of infection (58.7%). Pre-OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17-6.60, P=0.02), pre-OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24-6.19, P=0.012), and pre-OLT C3 hypocomplementemia (RR 3.02, CI=1.21-7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.

Total gastrectomy for type 1 gastric carcinoid: an unusual surgical indication?

Gastric carcinoid is a relatively rare neoplasm with peculiar features which differentiate it from the intestinal and pulmonary carcinoid and, obviously, from gastric adenocarcinoma. Gastric carcinoids are divided into three different types: Type 1, associated with gastric atrophy and megaloblastic anemia; Type 2, associated with Zollinger-Ellison syndrome within a type 1 multiple endocrine neoplasia (MEN); and Type 3, sporadic tumor not associated with other lesions, particularly invasive and with poor prognosis. Type 1 carcinoid is usually asymptomatic and casually detected at endoscopy due to aspecific symptoms or to screening in patients with atrophic gastritis. It is generally small, multifocal and located in the gastric fundus, has no tendency for vascular invasion and is associated with a benign course. Therefore, the recommended treatment, for lesions < 10 mm and in a number < 5, is endoscopic resection with strict follow-up. We report a case of a woman with a type 1 gastric carcinoid in which, for the presence of an extended micro-polyposis of the fundus a total gastrectomy was necessary for treatment. Pathology revealed vascular invasion at the level of the major lesion of 8 mm of diameter. In conclusion this finding, unknown before surgery, emphasizes the need for careful assessment also in the presence of apparently less important gastric carcinoid lesions.

Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis.

Endoglin, a transforming growth factor (TGF)-beta1 co-receptor, has been associated with renal and cutaneous fibrosis, as overexpression of this protein has been observed in biopsies from patients with glomerulosclerosis and scleroderma, respectively. Our aim was to evaluate whether endoglin may be associated with hepatic fibrosis featuring chronic hepatitis C virus (HCV) infection. Fifty-two anti-HCV+ patients, five anti-HCV- patients and 27 healthy subjects were studied. Western blot and immunohistochemistry were used to quantify the expression levels of endoglin and TGF-beta1 in liver biopsy samples, and serum concentrations of endoglin and hyaluronic acid were determined by enzyme-linked immunosorbent assays (ELISAs). In patients with advanced fibrosis, intrahepatic expression levels of endoglin and TGF-beta1 were significantly higher than those in patients with early fibrosis (mean: 3- and 5.8-fold, respectively) and normal liver (mean: 3.9- and 12-fold, respectively). Interestingly, activated hepatic stellate cells as well as portal and septal myofibroblasts expressed endoglin. Serum levels of endoglin were also significantly higher in patients with advanced fibrosis than in those with early fibrosis (55.5 +/- 1.6 vs 47.5 +/- 0.9 ng/mL, P < 0.001), showing a positive correlation with serum hyaluronic acid concentrations (r = 0.57, P = 0.01). In conclusion, increased intrahepatic endoglin and TGF-beta1 expression is significantly associated with progressive hepatic fibrosis in chronic HCV infection. Circulating endoglin levels are elevated in HCV patients showing a significant correlation with histological and serum markers of hepatic fibrosis. These data suggest an active role for endoglin in the fibrotic process featuring chronic HCV infection.

[Clinical heterogeneity and distinct outcomes in hepatic epithelioid hemangioendothelioma]. / Heterogeneidad clínica y evolutiva del hemangioendotelioma epitelioide hepático.

Epithelioid hemangioendothelioma is an infrequent mesenchymal tumor of unknown etiology and variable clinical symptoms. It usually affects black, middle-aged women. The most frequent symptoms are right hypochondrium pain, abdominal discomfort and constitutional syndrome with progressive liver damage. Diagnosis is difficult and detailed pathological analysis is required. Controlled clinical studies are lacking and there are no factors that predict the clinical course or serve as a guide to the most effective treatment. We report 3 cases with distinct clinical course ranging from clinical stability to dissemination and death. Treatment differed in the three patients.

Intraluminal brachytherapy without stenting in intrahepatic papillary cholangiocarcinoma: a case report.

A 46-year-old female patient, with mild cholestasis by a large papillary cholangiocarcinoma involving the left hepatic duct, received intraluminal brachytherapy (50 Gy at 1 cm from the source axis) with the aim to relieve biliary obstruction without stent positioning. The patient presented with haemobilia and vegetant lesions in the left main biliary duct, and thus she had a high risk of early stent obstruction. Eighteen months after the treatment the patient presented tumour progression in the controlateral hepatic lobe, but had a patent left hepatic duct, without signs of cholestasis and/or cholangitis. Based on this and other published reports, intraluminal brachytherapy may be tested in a setting different from standard setting with the aim to safely palliate jaundice in patients with intraductal tumour growth in the biliary tract.

Gene expression profile of T-cell-specific chemokines in human hepatocyte-derived cells: evidence for a synergistic inducer effect of cytokines and hepatitis C virus proteins.

Increased levels of chemokines (CK) in chronic hepatitis C virus (HCV) infection have been found. Given that NS5A and core can function as transcriptional transactivators, we aimed to determine whether these HCV proteins might induce CK gene expression in human hepatocyte-derived cells. We assessed (i) regulated upon activation, normal T cells expressed and activated (RANTES), interferon gamma-inducible protein-10 (IP-10), and monokine induced by interferon-gamma (MIG) mRNA levels in NS5A and core stably transfected Chang liver (CHL) cells, stimulated or not with a cytokine mixture (CM), by reverse transcriptase-polymerase chain reaction (RT-PCR) and (ii) quantitative enzyme-linked immunosorbent assay (ELISA) measurements of these CK in the supernatants of CHL cells. Induction of RANTES transcripts in resting HCV-transfected cells was clearly observed, being augmented fourfold in resting NS5A-transfected cells and threefold in resting core-transfected cells over that in resting mock-transfected (control) cells, as well as to a similar extent in CM-stimulated NS5A- and core-transfected cells. Increased RANTES secretion followed the same pattern observed for mRNA expression. Both IP-10 and MIG, such as mRNA and protein levels, were undetectable in resting HCV-transfected and -untransfected cells, whereas IP-10 and MIG mRNA expression was increased by seven- and fivefold in CM-stimulated NS5A-transfected cells and by 10- and 3.5-fold in CM-stimulated core-transfected cells, respectively, above that in CM-stimulated control cells. IP-10 and MIG secretion was enhanced by 2.6- and threefold in CM-stimulated NS5A-transfected cells and by 3.6-fold and 3.7-fold in CM-stimulated core-transfected cells, respectively over that in CM-stimulated control cells. These results demonstrate that NS5A and core proteins, alone or by the synergistic effect of cytokines, are capable of upregulating RANTES, IP-10 and MIG gene expression in cultured human hepatocyte-derived cells.

Is the chronologic age a contra-indication for surgical palliation of unresectable periampullary neoplasms?

METHODS: Early and late results of surgical palliation for unresectable periampullary neoplasms were evaluated in 24 patients older than 70 years and compared with the same results obtained from 33 younger patients. The two groups of patients were comparable, except for age. Biliary bypass associated to gastric bypass was the most common performed procedure. RESULTS: No significant differences in the results (morbidity, mortality, and outcome) were found in the two groups of patients. In addition, the results of palliative surgery in the elderly were compared with those obtained from a comparable group of 35 patients palliated with endoscopic stent insertion: surgical palliation resulted in better long-term results. CONCLUSIONS: This study provides evidence that the chronologic age is not a contra-indication for surgical palliation of periampullary neoplasms and that surgery provides a better quality of residual life.

Increased intrahepatic cyclooxygenase 2, matrix metalloproteinase 2, and matrix metalloproteinase 9 expression is associated with progressive liver disease in chronic hepatitis C virus infection: role of viral core and NS5A proteins.

BACKGROUND: Cyclooxygenase 2 (COX-2) and matrix metalloproteinases (MMPs) have been implicated in tissue injury and fibrogenesis in animal models but little is known regarding their role in hepatitis C virus (HCV) related liver disease in humans. AIMS: To characterise the intrahepatic expression pattern of COX-2 and MMPs in chronic HCV infection and determine whether HCV core and NS5A proteins could promote their expression in cultured hepatocyte derived cell lines. PATIENTS: Thirty two anti-HCV+ and 10 anti-HCV- patients were studied. METHODS: Western blot, reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunohistochemistry were used to assess the expression pattern of COX-2 and MMPs in liver biopsy samples from all patients. COX-2 gene expression and MMP-9 protein levels were also determined by immunoblot, RT-PCR, and luciferase assays in core and NS5A transfected hepatocyte derived cells. RESULTS: The intrahepatic expression level of COX-2, MMP-2, and MMP-9 was significantly higher in HCV+ than in HCV- patients, increasing with the fibrotic stage of liver disease. We further demonstrated that COX-2 mRNA, protein, and activity were induced in resting and activated core and NS5A transfectants. Both viral proteins induced transcriptional activity of the COX-2 gene promoter whereas core, but not NS5A, exerted an inducer effect on MMP-9 protein levels in cultured hepatocyte derived cells. CONCLUSIONS: Intrahepatic COX-2, MMP-2, and MMP-9 overexpression is associated with progressive hepatic fibrosis in chronic HCV infection, suggesting their pathogenic role in fibrogenesis. HCV core and NS5A proteins were able to upregulate COX-2 and MMP-9 gene expression in hepatocyte derived cells, providing a potential mechanism for hepatic fibrosis during chronic HCV infection.

Autonomic neuropathy is associated with hemodynamic instability during human liver transplantation.

INTRODUCTION: End-stage liver disease is frequently associated with autonomic neuropathy (AN). The hemodynamic changes during liver transplantation (LT) require an adequate autonomic response to maintain cardiovascular stability. PATIENTS AND METHODS: Forty-one patients undergoing LT were evaluated for the influence of AN on the evolution after LT. AN was previously evaluated by seven cardiovascular tests assessing sympathetic (Sy) or parasympathetic (P) function. Patients were classified as absent (A), early (E), or definite dysfunction (D). A hemodynamic study was performed before and after vascular clampings. The analysis included the duration of LT, transfusion requirements, intra-operative artenal hypotensive episodes, incidence of postreperfusion syndrome (PRS), cardiac arrhythmias and vasoactive drug requirements. RESULTS: The hyperdynamic circulation worsened during surgery in D patients, as shown by a significantly increased cardiac output and a significantly decreased systemic vascular resistance. The incidence of PRS was greater in the AN group. Arterial hypotension during the neohepatic period was more frequent among patients with AN, more frequently requiring vasoconstrictor and inotropic therapy. CONCLUSIONS: AN is associated with hemodynamic impairment and with increased vasoactive drug requirements during liver transplantation, probably associated with impaired reflex vasoconstrictor responses to surgical manipulations and changes of blood volume. AN may be associated with a greater surgical risk during LT. Preoperative evaluation of AN may select a high-risk population of LT recipients.