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Background Cardiac magnetic resonance (CMR) examinations have an essential role in the diagnosis of myocardial diseases with left ventricular (LV) hypertrophy; however, limited data are available from CMR-based feature-tracking strain analysis in this patient population. The aim of our study was to investigate the differential diagnostic and prognostic importance of feature-tracking strain analysis in patients with LV hypertrophy caused by myocardial disease. Methods We investigated 404 patients who underwent CMR examination and were diagnosed with myocardial disease causing LV hypertrophy. Hypertrophic cardiomyopathy (HCM) was detected in 330 patients, cardiac amyloidosis (CA) in 46 patients, Fabry disease (FD) in 12 patients, and endomyocardial fibrosis (EMF) in 16 patients. LV strain analysis was performed with feature-tracking. Global longitudinal (GLS), circumferential (GCS) and radial (GRS) LV strain parameters were measured. Strain values for the six basal, six midventricular, and five apical segments were averaged to obtain regional longitudinal and circumferential strain values (basal LS, midventricular LS, apical LS, basal CS, midventricular CS, apical CS). The apex-to-base regional LS and CS ratios were calculated as apical LS/basal LS and apical CS/basal CS, respectively. To assess global dyssynchrony, mechanical dispersion (MD) was measured. The all-cause mortality of the patients was analyzed. Results In the differentiation of CA from HCM, GLS had the highest sensitivity with a cutoff of more than −23%, and basal LS and basal CS had the highest specificity with a cutoff of more than −16% and −38%, respectively (p Conclusions Myocardial diseases with left ventricular hypertrophy have remarkable differences in CMR-based strain characteristics which can be helpful in the differential diagnosis and provides incremental information on adverse outcomes. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Development and Innovation Fund of Hungary, Ministry for Innovation and Technology in Hungary

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This study was financed by the Ministry of Innovation and Technology NRDI Office within the framework of the Artificial Intelligence National Laboratory Program. LS is supported by the EACVI Research Grant 2021. Introduction Cardiac adaptation due to regular and intense exercise is a well-known phenomenon. Cardiac magnetic resonance (CMR) imaging is a well suited, highly reproducible technique that has a vital role in differentiating physiological adaptation and pathological alterations. Native T1 and T2 mapping enable the quantitative assessment of tissue characteristics without the administration of contrast material. These techniques are increasingly used in studies aiming to consider subtle differences. However, the sex-and training-dependence of native T1 and T2 mapping values remains incompletely understood. Purpose We aimed to describe the differences in native T1 and T2 mapping among healthy athletes and less active individuals. Methods We enrolled healthy elite athletes (n=88, 56 male, 25±5 years) and healthy volunteers (n=82, 46 male, 25±3 years) to undergo CMR examinations at our Centre. Healthy elite athletes performed high sports activity levels (>10 hours/week) and competed nationally or internationally. Sex- and age-matched healthy volunteers engaged in ≤6 hours/week of sports activity. Standardized CMR protocol included short- and long-axis cine images covering the entire left (LV) and right (RV) ventricle and native T1 and T2 mapping in basal, midventricular and apical slices. Results Athletes had consistently higher LV and RV volumes and mass indexes compared to healthy volunteers (p Conclusion Our study demonstrates the importance of sex-matched controls in CMR studies evaluating mapping parameters. Moreover, the consideration of exercise load seems paramount in the case of T1 mapping.

Introduction: The cardiovascular effects of COVID-19 in elite athletes is still a matter of intense scientific debate. Hypothesis: We sought to perform a comprehensive echocardiographic characterization of post-COVID athletes by comparing them to a non-COVID athlete cohort. Methods: 107 elite athletes with COVID-19 were prospectively enrolled (P-CA; 23±6 years, 23% female) 107 healthy athletes were selected as a control group using propensity score matching (N-CA). All athletes underwent 2D and 3D echocardiography. Left (LV) and right ventricular (RV) end-diastolic volumes (EDVi) and ejection fractions (EF) were quantified. To characterize LV longitudinal deformation, 2D global longitudinal strain (GLS) and the ratio of free wall versus septal longitudinal strain (FWLS/SLS) were also measured. To describe septal flattening (SF - frequently seen in P-CA), LV eccentricity index (EI) was calculated. Results: P-CA and N-CA athletes had comparable LV and RVEDVi (P-CA vs N-CA; 77±12 vs. 78±13mL/m2; 79±16 vs 80±14mL/m2). P-CA had significantly higher LVEF (58±4 vs 56±4%, p Conclusions: COVID-19 infection might be frequently associated with a constriction-like physiology in elite athletes.

Establishing the diagnosis of sarcoidosis most often requires biopsy and histopathologic evaluation, since there is no single marker with sufficient specificity and sensitivity for the disease. Our aims were to determine and compare the diagnostic accuracies of several potential biomarkers and to develop a combined biomarker analysis tool for the diagnosis of sarcoidosis. 133 healthy individuals and 104 patients with suspected sarcoidosis and diagnostic thoracic surgery were enrolled into this study. Histopathologic results were contrasted to biomarker levels of chitotriosidase (CTO), serum amyloid-A (SAA), soluble interleukin-2 receptor (sIL-2R), lysozyme (LZM) or angiotensin converting enzyme (ACE). Sarcoidosis was confirmed by histopathology in 69 patients. CTO activity, sIL-2R concentration and ACE activity could discriminate between sarcoidosis and control patients, while SAA and LZM concentrations could not. A new combined parameter, which was derived from the multiplication of ACE by CTO activities (double product) showed the best diagnostic accuracy in this clinical study: (AUC = 0.898, sensitivity: 90.5%, specificity: 79.3%, positive and negative predictive values: 90.5% and 79.3%, respectively). Sarcoidosis can be diagnosed with the combined analysis of ACE and CTO activities more accurately than with single serum biomarkers in the absence of invasive biopsy in the majority of cases with pulmonary manifestation of sarcoidosis.

espanolLa “europeizacion” de las esferas publicas nacionales es una cuestion de crear un espacio mediatico discursivo dentro de la UE. Hay fuerzas de convergencia, como redes en el espacio digital. Al mismo tiempo, hay fuerzas contrarias, un creciente nacionalismo y populistas que critican las elites a “Bruselas”. Aparentemente, la vision de una esfera publica europea comparte su suerte con el proyecto Europeo: despues de anos de crisis, el optimismo se convirtio en desilusion. Utilizando la cobertura mediatica de las elecciones de la UE de 2019 en siete paises europeos (57.943 articulos de Alemania, Hungria, Italia, Polonia, Portugal, la Republica Checa y el Reino Unido), dibujamos cuadro de un publico heterogeneo de la UE. Resulta claramente que la europeizacion horizontal y vertical requieren interpretaciones diferenciadas. Un alto grado de europeizacion horizontal indica una cobertura mediatica convergente y pro-europea (como Alemania o Portugal), un alto grado vertical puede indicar un publico polarizado o un panorama mediatico poco libre (como el Reino Unido o Hungria). EnglishThe issue of the Europeanisation of national public spheres is a question as to how a discursive media space can be created within the EU. There are forces of convergence at work, such as networking within the borderless digital space. At the same time, there are counterforces: increasing nationalism and populists who identify ‘Brussels’ as a target for their criticism of elites. The vision of a European public sphere appears to share the same fate as the European project as such; as a result of years of crisis, optimism has given way to disillusion. Using coverage of the 2019 EU elections in seven European countries (a total of 57,943 articles from Germany, Hungary, Italy, Poland, Portugal, the Czech Republic, and the UK), we draw a picture of a heterogeneous EU public. What is particularly clear is that the phenomena of horizontal and vertical Europeanisation require more nuanced interpretations. While a high degree of horizontal Europeanisation indicates convergent and pro-European media coverage (as in the cases of Germany and Portugal), a high degree of vertical Europeanisation may indicate polarised publics or an unfree media landscape (as in the UK and Hungary). From a methodological point of view, the study shows that a combination of computational content analysis and international cooperation between scientists can advance research into the European public.

Дано решение открытой проблемы олимпиады по криптографии NSUCRYPTO-2018: показано, что не существует ортогональных массивов OA (16L, 11, 2, 4) с L = 6 и 7. Этот результат позволяет определить минимальные веса некоторых корреляционно-иммунных булевых функций высокого порядка.

Background Administration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. Objective To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy. Methods Based on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro. Results Intranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab. Conclusion Intranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.

The authors investigated the possibility of the presence of VTEC strains in improperly pasteurized milk samples. A total of 64 Escherichia coli strains were isolated from 135 pasteurized milk samples originating from the same producer. The examined isolates contained 29 haemolysin-, 9 colicin- and 5 aerobactin-producing strains, but the investigations concerning heat-resistant and heat-sensitive toxins gave negative results.Six O128-type E. coli strains exerted a cytotoxic effect on the VERO cell line; 5 of them contained H12 antigen, while one could not be typed. Four of the 6 verocytotoxin-producing strains belonged in phage group 20, one in phage group (2)3(7), and one in phage group 4; four strains were of B3, one of A1, and one of A1(A2) phage type.Because of a technical failure the milk was pasteurized at 69 °C for 15 s, which is 2 °C less than required. The results underline the importance of the appropriate pasteurization temperature, as otherwise the milk may contain verocytotoxin-producing E. coli, which is a potentially great hazard for public health.

Conditions during coronary artery bypass grafting (CABG) performed on beating heart (off-pump) are more physiological than using extracorporeal perfusion (on-pump). The present study aims to examine the hemorheological aspects of the two techniques. Blood samples were taken from patients undergoing on-pump (n = 25) and off-pump (n = 22) CABG, upon arrival to the operating theatre, after 20 and 40 minutes during the operation, after closing the thorax, on the 1st and 2nd postoperative days, and during the 2nd and 6th month control check-ups. Hematocrit (Hct), plasma and whole blood viscosity (PV, WBV; Hevimet 40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne RBC aggregometer, LORCA) and deformability (LORCA, Carat FT-1 filtrometer), and platelet aggregation (Carat TX4 aggregometer) were determined. The morphology of red blood cells was investigated by scanning electron microscopy (SEM). Hct, PV, WBV and RBC aggregation decreased significantly during the early phase of the surgery, they started to recover during the postoperative period, and reached the baseline values by the 2nd and 6th month control check-ups. These parameters were significantly lower in samples taken after 20 and 40 minutes in the on-pump group. SEM showed rather damaged and malformed cells in case of on-pump surgery. Ektacytometry showed no significant difference, but RBC deformability was impaired during on-pump surgery when measured by filtrometry. The decrease in platelet aggregation was more pronounced by the end of surgery in case of on-pump technique. During CABG rheological parameters change less when using the off-pump method, and mechanical damage of RBCs are also smaller. The off-pump technique seems to be favorable from a hemorhelogical point of view.

To compare three different ultrasound-guided injections for chronic tennis elbow.Assessor-blinded, randomized controlled comparative trial.44 patients with clinically diagnosed tennis elbow, confirmed by Doppler ultrasound, received under ultrasound guidance, a single corticosteroid injection (n=14), or two injections (separated by 4 weeks) of either autologous blood (n=14) or polidocanol (n=16). Clinical and ultrasound examination was performed at baseline, 4, 12 and 26 weeks.Complete recovery or much improvement was greater for corticosteroid injection than autologous blood and polidocanol at 4 weeks (p0.001, number needed to treat 1 (95% CI 1-2)). In contrast, at 26 weeks corticosteroid was significantly worse than polidocanol (p=0.004, number needed to harm 2 (1-6)). Recurrence after corticosteroid injection was significantly higher than autologous blood or polidocanol (p=0.007, number needed to harm 2 (1-4)). Corticosteroid injection produced greater reduction in tendon thickness and vascularity than autologous blood at 4 weeks only. Compared to autologous blood, polidocanol reduced tendon thickness at 4 and 12 weeks and reduced echogenicity and hyperaemia after 12 or 26 weeks respectively.Injections of corticosteroid cannot be recommended over polidocanol or autologous blood, because despite beneficial short-term effect there were inferior long-term effects. Whether polidocanol or autologous blood injections are effective is unknown, especially as their global effect profiles are not unlike previously reported for wait-and-see.

For understanding local and regional seed dispersal and plant establishment processes and for considering the ecotypes and other forms of specific variability, hard data of locally or regionally measured traits are necessary. We provided newly measured seed weight data of 193 taxa, out of which 24 taxa had not been represented in the SID, LEDA or BiolFlor databases. Our new measurements and formerly published data of locally collected seed weight records together covers over 70% of the Pannonian flora. However, there is still a considerable lack in seed weight data of taxonomically problematic genera, even though they are represented in the Pannonian flora with a relatively high number of species and/or subspecies (e.g. Sorbus, Rosa, Rubus, Crataegus and Hieracium). Our regional database contains very sporadic data on aquatic plants (including also numerous invasive species reported from Hungary and neighbouring countries) and some rare weeds distributed in the southwestern part of the country. These fact...

Galectins are a family of animal lectins with an affinity for beta-galactosides. They are differentially expressed by various tissues and appear to be functionally multivalent, exerting a wide range of biological activities both during development and in adult tissue. Galectin-7, a member of this family, contributes to different events associated with the differentiation and development of pluristratified epithelia. It is also associated with epithelial cell migration, which plays a crucial role in the re-epithelialization process of corneal or epidermal wounds. In addition, recent evidence indicates that galectin-7, designated as the product of the p53-induced gene 1 (PIG1), is a regulator of apoptosis through JNK activation and mitochondrial cytochrome c release. Defects in apoptosis constitute one of the major hallmarks of human cancers, and galectin-7 can act as either a positive or a negative regulatory factor in tumour development, depending on the histological type of the tumour.

Ochratoxin A is a mycotoxin produced by Aspergillus and Penicillium species. This mycotoxin is a common contaminant of various food products including cereal products, spices, dried fruits, coffee, beer and wine. Besides cereal products, beer and wine contribute significantly to ochratoxin exposure of humans. We examined the ochratoxin content of Hungarian wines and beers using an immunochemical technique. The detection limit of this technique is 0.01mg l-1. Altogether 65 wine and 25 beer samples were analysed. The presence of ochratoxin A was confirmed by HPLC in positive samples. Ochratoxin A was detected in 97.7% of wines, with ochratoxin concentrations ranging from 0 to 0.533mg l-1. The mean ochratoxin A concentration in wines was 0.110mg l-1. Only one of the Hungarian wines examined contained more than 0.5mg l-1ochratoxin A, the previously suggested EU limit for wine. Our data indicate that red wines are more frequently contaminated, and have higher mean ochratoxin contamination (0.117mg ml-1) than w...

The etiology of colorectal cancer (CRC) involves the interaction of cell molecular changes and environmental factors, with a great emphasis on diet components. But the paths connecting lifestyle characteristicas and the colorectal carcinogenesis remain unclear. Several risk factors are commonly found in western diets, such as high concentrations of fat and animal protein, as well as low amounts of fiber, fruits and vegetables. A large number of experimental studies have found a counteractive effect of fiber on neoplasia induction, especially in relation to fermentable fiber (wheat bran and cellulose). Epidemiological correlation studies have also indicated that a greater ingestion of vegetables, fruit, cereal and seeds is associated to a lower risk for colorectal neoplasia. Moreover, beneficial properties of fiber (especially from vegetable sources) were documented in more than half of case-control studies. Nevertheless, recent epidemiological data from longitudinal and randomized trials tended not to support this influence. Future research should evaluate what sources of fiber provide effective anti-neoplasic protection, carrying out interventional studies with specific fibers for longer periods. Red meat, processed meats, and perhaps refines carbohydrates are also implicated in CRC risk. Recommendantions to decrease red meat intake are well accepted, although the total amount and composition of specific fatty acids may have distinct roles in this setting. Current evidence favors the substitution of long and medium-chain fatty acids and arachidonic acid for short-chain fatty acids and eicosapentaenoic acid. Excess boy weight and excess energy intake inducing hyperinsulinemia have been also associated to CRC, as well as personal habits such as physical inactivy, high alcohol consumption, smoking and low consumption of folate and methionine. Thus, current recommendations for decreasing the risk of CRC include dietary measures such as increased plant food intake; the consumption of whole grains, vegetables and fruits; and reduced red meat intake.La etiología del cáncer colorrectal (CCR) implica la interacción entre los cambios celulares moleculares y los factores ambientales, con un gran énfasis sobre los componentes de la dieta. Pero los caminos que conectan las características del estilo de vida con la carcinogénesis siguen siendo inciertos. En las dietas occidentales se encuentran, habitualmente, diversos factores de riesgo como las concentraciones elevadas de grasa y proteínas de origen animal, así como cantidades bajas de fibra, frutas y vegetales. Un gran número de estudios experimentales han encontrado que la fibra contrarresta la inducción de neoplasia, especialmente en relación con la fibra fermentable (salvado de trigo y celulosa). Los estudios de correlación epidemiológica también han indicado que una mayor ingestión de vegetales, frutas, cereales y semillas se asocia con un riego menor de neoplasia colorrectal. Además, en más de la mitad de los estudios de casos-control, se documentaron las propiedades beneficiosas de la fibra (especialmente de origen vegetal). Sin embargo, los datos epidemiológicos recientes de estudios longitudinales y de distribución aleatoria no tendían a apoyar esta influencia. La investigación futura debería evaluar qué fuentes de fibra proporcionan una protección antineoplásica realizando estudios de intervención con fibras concretas, durante periodos más prolongados. Las carnes rojas y las procesadas, y quizás los hidratos de carbono refinados, también están implicadas en el riesgo de CCR. Están bien aceptadas las recomendaciones para disminuir la ingestión de carne roja, aunque la cantidad total y la composición de ácidos grasos concretos pueden tener efectos distintos en este contexto. La evidencia actual se decanta por la sustitución de los ácidos grasos de cadena larga y media y del ácido araquidónico por los ácidos grasos de cadena corta y por el ácido eicosanopentanoico. El exceso de peso corporal y el exceso de aporte de energía que induce una hiperinsulinemia también se han relacionado con el CCR, así como los hábitos personales como la inactividad física, el consumo elevado de alcohol, el tabaquismo y el consumo bajo de folatos y metionina. Por lo tanto, las recomendaciones actualespara disminuir el riesgo de CCR incluyen medidas dietéticas como aumentar los alimentos de origen vegetal, el consumo de granos completos, vegetales y frutas y reducir el consumo de carnes rojas.

Inflammatory Bowel Diseases - ulcerative colitis and Crohn’s disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.Las enfermedades inflamatorias del intestino -colitis ulcerosa y enfermedad de Crohn- son enfermedades crónicas de causa desconocida. La disminución de la ingesta, la malabsorción, la pérdida acelerada de nutrientes, el aumento de los requerimientos y las interacciones entre medicamentos y nutrientes determinan carencias nutricionales y funcionales que obligan a una corrección mediante terapia nutricional. Los objetivos de los distintos tipos de terapia nutricional comprenden la corrección de las alteraciones nutricionales y la modulación de la respuesta inflamatoria para modificar la actividad mórbida. La alimentación puede mejorar algunos aspectos pero, debido al coste y a las complicaciones de este tratamiento, exige una cuidadosa selección. Se ha empleado la nutrición parenteral total para corregir y prevenir las alteraciones nutricionales y fomentar el reposo del intestino durante la actividad, sobre todo en los casos de fístulas digestivas con un elevado drenaje. Su uso debe reservarse a los pacientes que no toleren la nutrición enteral. La nutrición enteral induce una remisión clínica eficaz entre los adultos y promueve el crecimiento infantil. La investigación reciente se ha centrado en el uso de nutrientes específicos como medios esenciales de tratamiento. Si bien en algunos informes se ha señalado que la glutamina, los ácidos grasos de cadena corta, los antioxidantes y la inmunonutrición con ácidos grasos omega-3 suponen una alternativa terapéutica importante para el tratamiento de las enfermedades inflamatorias del intestino, los efectos beneficiosos descritos todavía no se han reflejado en la práctica clínica. La eficacia real de estos nutrientes obliga a una evaluación más cuidadosa a través de ensayos prospectivos y aleatorizados.

Ileal pouch-anal anastomosis was an important advancement in the treatment of ulcerative colitis. The aim of this study was to determine whether early complications of ileal pouch-anal anastomosis in patients with ulcerative colitis are associated with poor late functional results. PATIENTS AND METHODS: Eighty patients were operated on from 1986 to 2000, 62 patients with ileostomy and 18 without. The early and late complications were recorded. Specific emphasis has been placed on the incidence of pouchitis with prolonged follow-up. RESULTS: The ileostomy was closed an average of 9.2 months after the first operation. Fourteen patients were excluded from the long-term evaluation; 6 patients were lost to regular follow-up, 4 died, and 4 patients still have the ileostomy. Of the 4 patients that died, 1 died from surgical complications. Early complications after operation (41) occurred in 34 patients (42.5%). Late complications (29) occurred in 25 patients as follows: 16 had pouchitis, 3 associated with stenosis and 1 with sexual dysfunction; 5 had stenosis; and there was 1 case each of incisional hernia, ileoanal fistula, hepatic cancer, and endometriosis. Pouchitis occurred in 6 patients (9.8%) 1 year after ileal pouch-anal anastomosis, 9 (14.8%) after 3 years, 13 (21.3%) after 5 years, and 16 (26.2%) after more than 6 years. The mean daily stool frequency was 12 before and 5.8 after operation. One pouch was removed because of fistulas that appeared 2 years later. CONCLUSIONS: Ileal pouch-anal anastomosis is associated with a considerable number of early complications. There was no correlation between pouchitis and severe disease, operation with or without ileostomy, or early postoperative complications. The incidence of pouchitis was directly proportional to duration of time of follow-up.A anastomose íleo-anal com reservatório ileal foi um importante avanço no tratamento da retocolite ulcerativa. O objetivo deste trabalho foi determinar se os maus resultados funcionais tardios estariam relacionados às complicações precoces da anastomose íleo-anal com reservatório ileal em doentes com retocolite ulcerativa. MATERIAL E MÉTODO: Oitenta doentes foram operados entre 1986 e 2000, 60 com ileostomia de proteção e 18 sem. Os doentes foram avaliados quanto a incidência de complicações pós-operatórias precoces e tardias. Enfatizou-se a incidência de bolsite no pós-operatório prolongado. RESULTADO: A ileostomia foi fechada em média 9,2 meses após a primeira operação. Quatorze doentes foram excluídos da avaliação tardia: seis perderam o seguimento e quatro faleceram. Quatro doentes permanecem com a ileostomia. Trinta e quatro doentes (42,5%) apresentaram 41 complicações precoces. Vinte e cinco apresentaram 29 complicações tardias: 16 bolsites, três associadas a estenose e uma a disfunção erétil; cinco estenoses e uma de cada das seguintes: hérnia incisional, fístula íleoanal, câncer hepático e endometriose. Seis doentes apresentaram bolsite um ano após a anastomose íleoanal com reservatório ileal (9,8%), nove (14,8%) após três anos, 13 (21,3%), após cinco anos e 16 (26,2%) após seis anos.A freqüência diária média de evacuação era de 12 antes e de 5,8 após a operação.Um reservatório foi removido devido ao aparecimento de fístulas dois anos depois. CONCLUSÃO: A anastomose íleoanal com reservatório ileal está associada com número considerável de complicações. Não há correlação entre bolsite e doença grave, operação com ou sem ileostomia ou complicações pós-operatórias imediatas. A incidência de bolsite foi diretamente proporcional ao tempo de seguimento.

Inflammatory Bowel Diseases - ulcerative colitis and Crohn's disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn's disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.As doenças inflamatórias intestinais - retocolite ulcerativa inespecífica e doença de Crohn - são afecções inflamatórias gastrointestinais crônicas de causa ainda desconhecida. Caracterizam-se por diarréia crônica, malabsorção, síndrome do intestino curto, disfunção da barreira mucosa e processo inflamatório intestinal, fatores que determinam deficiências nutricionais e funcionais que ressaltam a importância da terapia nutricional em seu tratamento. As diversas formas de terapia nutricional visam corrigir os distúrbios nutricionais e modular à resposta inflamatória, podendo, desta forma, influir na atividade da doença. A nutrição parenteral total tem sido usada para corrigir os distúrbios nutricionais e proporcionar repouso intestinal na doença ativa. Seu uso deve ser reservado a pacientes que não podem tolerar a nutrição enteral. A nutrição enteral é efetiva em induzir remissão clínica da doença em adultos e promover crescimento em crianças. Devido à baixa incidência de complicações e menor custo, a nutrição enteral deve ser opção preferencial à nutrição parenteral total quando possível. Ambas apresentam igual efetividade na terapia primária na remissão da Doença de Crohn ativa. Embora a terapia nutricional possa melhorar a evolução de muitos pacientes, é necessária uma seleção criteriosa devido a seus custos e complicações, especialmente naqueles que requerem nutrição parenteral total. Recentes pesquisas têm se dedicado ao uso de nutrientes como agentes terapêuticos primários. A imunonutrição com ácidos graxos ômega-3 se constitui numa importante alternativa terapêutica no manuseio das doenças inflamatórias intestinais, modulando o processo inflamatório e modificando o perfil de produção de eicosanóides. Entretanto, a real eficácia deste e outros nutrientes (glutamina, ácidos graxos de cadeia curta) ainda necessitam de novas avaliações por estudos prospectivos, controlados e randomizados.

We have studied the ethyl acetate fraction of the methanolic extract of the root barks of Calotropis procera (Asclepiadaceae) from Egypt. Bioassay-directed fractionation and final purification of the extract resulted in the identification of a new cardenolide glycoside named proceraside A (1) together with two known compounds, frugoside (2) and calotropin (3). Their structures were elucidated by extensive NMR studies and mass spectrometric data. The in vitro cytotoxicity of the isolated compounds was evaluated against A549 non-small cell lung cancer, U373 glioblastoma and PC-3 prostate cancer cell lines. They showed potent activity against the tested cancer cell lines with IC50 ranging from 0.005 to 0.3 μg/mL. Cisplatin was used as positive control.

A computer-assisted microscope analysis of Feulgen-stained nuclei was carried out on a series of 50 nasal polyps in order to try to identify specific biological subgroups. The present series of 50 nasal polyps includes single polyps both associated (n=9) and unassociated (n=9) with allergy and diffuse polyposis both associated (n=7) and unassociated (n=9) with allergy, cystic fibrosis (n=9) and ASA (aspirin-sinusitis-asthma) related polyposis (n=7). The computer-assisted microscope analysis provides 36 quantitative variables which include 1 variable describing proliferative activity, 9 describing the nuclear desoxyribonucleic acid distribution (DNA ploidy level) and 26 describing nucleus morphology, i.e. its size and chromatin pattern. The results show that the methodology proposed here enabled four major groups of nasal polyps to be identified, i.e. diffuse polyposis associated with allergy, cystic fibrosis-related polyposis, single polyps both associated and unassociated either with allergy and a fourth group including diffuse polyposis not associated with allergy and ASA-related polyposis. These four groups of nasal polyps differed markedly in their morphonuclear characteristics, but not in the proliferative activity- and DNA ploidy- related variables.

Pelvic recurrence following conventional rectal resection for cancer is common. Preoperative iradiation has been shown in prospective randomized studies to halve this risk.This multiinstitutional study aimed to assess the necesity of total mesorectal excision in rectal cancer.Pathological resections from 50 consecutive patients with adenocarcinoma of the rectum within 12 cm of the anal verge who underwent currative resection incorporating total mesorectal excision were examined. The resection specimen was examined by one of two pathologists. Some 50 total mesorectal excision specimens were examined following rectal excision for cancer. Some 38 had total mesorectal excision as a component of a low anterior resection and 12 with abdomino-perineal resection. "Cure" was defined as absence of metastatic disease and the excision of entire macroscopic tumor tissue with negative proximal and distal borders. TME was performed as described by Heald et al. The mesorectum was evaluated for lymph nodes and tumor deposists in three areas: deep to the tumor, in the proximal mesorectum and in the distal mesorectum.Six patients had Dukes A lesions. Of 21 patients with Dukes B tumors, five had discrete foci of adenocarcinoma in the mesorectum, with no evidence of lymph node metastasis. Dukes C lesions were more heterogeneous, but 12 out of 23 patients had distinct mesorectal deposists in addition to mesorectal node involvement. Circumferential margin involvement was rare, but mesorectal tumor deposits were present in 17 of 44 patients with pT3 tumors, and 23 of 44 had mesorectal nodal involvement. No patient with a pT2 tumor had mesorectal involvement. Failure to excise the mesorectum completely has the potential to leave gross or microscopic residual disease that may in theory predispose to local failure.Total mesorectal excision is necessary to avoid incomplete pathological evaluation of the mesorectum and understaging of rectal cancer.

A systematic and thus objective method is proposed to characterize astrocytic tumor aggressiveness. This method relies upon the combined use of a specific decisional algorithm (the decision tree) and 23 parameters which include 15 morphonuclear parameters describing the geometric, densitometric, and textural features of a cell nucleus, and 8 parameters describing the various levels of nuclear DNA content. These 23 parameters were objectively quantified by means of the digital cell image analysis of Feulgen-stained nuclei. This methodology was used to investigate whether it could be applied as a diagnostic tool. The biological model chosen included 12 cell lines adapted to grow in vitro and stemming from 4 astrocytomas (weakly malignant astrocytic tumors) and 6 glioblastomas (highly malignant ones). The 2 additional cell lines were from two medulloblastomas (MED) (2 highly malignant primitive neuro-ectodermal tumors). The results demonstrate unambiguously that it is actually possible to distinguish between low-grade and high-grade tumors on the basis of these parameters, which describe their morphonuclear features and the amount of their nuclear content. However, a clear-cut distinction between these different types of tumors can only be attained when a specific technique is used. In the present case this was the decision tree technique. We were not able to distinguish between these various histopathological groups when we used conventional statistical methods including the one-way-variance analysis of data or the carrying out of the X(2) test.

Wear of orthopaedic bearing materials, especially the ultra high molecular weight polyethylene (UHMWPe) component, is a leading clinical concern. The reported wear rates of typical bearing materials are subject to extremevariability due to various factors including the operating environment, measuring technique, testing protocol, and machine characteristics such as mechanical stiffness and vibration. Also, a lack of standardization in reporting pertinent information confounds this variability. This investigation characterized the performance of a wear testing device. Through vibrational analysis, an attempt was made to identify possible reasons for discrepancies in the reported wear testing results for orthopaedic biomaterials. Wear result variability was probably a combination of the vibration characteristics of the individual tester and uncertainties introduced by the wear measurements themselves. The effect of superimposed base vibrations on the pins was investigated. Characteristic frequencies of pin vibrations were linked to the dominant wear mechanisms in the orthopaedic tribological system.

cGMP has a short-term effect on smooth muscle tone and a longer-term effect on responses to chronic drug treatment or proliferative signals. cGMP-Phosphodiesterase type 5 (PDE5) hydrolizes cGMP, and the result is smooth muscle contraction. PDE5 is a relatively novel therapeutic target of various diseases, such as erectile dysfunction and pulmonary hypertension. The most intensively examined and marketed PDE5 inhibitor was sildenafil (Viagra) but recently vardenafil (Levitra) and tadalafil (Cialis) were launched with beneficial ADME parameters and PDE5 selectivity. The increasing interest in PDE5 inhibition made it reasonable to collect the available inhibitory data from the scientific literature and set up a structure-activity relationship study. Chemical structures of 438 compounds and their cGMP-PDE5 inhibitory data (IC50) were collected from recently published articles. In this paper physiology, regulation and inhibition of PDE5 (and briefly other PDE-s) are discussed and inhibitors are tabulated by the core structures. Finally, a general QSAR model built from these data is presented. All data used in the QSAR study were summarized in a Supplement (for description please see the online version of the article).

We studied the etiology of acute gastroenteritis in a village with a total population of approximately 6,000. This is the first study in Austria that has investigated a broad range of pathogens recovered from an unselected population of patients who had consulted general practitioners because of gastroenteritis. In 2007, all patients who visited one of three local general practitioners for acute gastroenteritis were invited to provide stool specimens to be tested for Salmonella, Shigella, Campylobacter, enterohemorrhagic Escherichia coli (EHEC) (mTSB enrichment [R-Biopharm] followed by toxin ELISA plus culture), enteropathogenic E. coli (EPEC), Yersinia, Vibrio cholerae, Clostridium difficile (toxin plus culture), rotavirus plus adenovirus (RIDA® Quick Rotavirus/Adenovirus Combi test), Giardia duodenalis plus Cryptosporidium parvum (RIDA® Quick Cryptosporidium/Giardia Combi test), astrovirus (ELISA), and norovirus (reverse-transcriptase PCR). Stool specimens were provided by 306 patients (161 female) with acute diarrhea. The ages of the patients ranged from 1 to 89 years (mean 37, median 36). Pathogens were detected in 71 (23.2%) patients, with incidence peaks in February and June. Norovirus accounted for 36.0% of positive results, C. difficile for 18.7%, rotavirus for 17.3%, Campylobacter for 9.3%, Salmonella for 6.6%, adenovirus for 5.4%, G. duodenalis and C. parvum for 2.7% each, and Yersinia enterocolitica for 1.3%. No cases of shigellosis or infection with EHEC, EPEC, or astrovirus were diagnosed. Viruses accounted for 58.7% of the 75 positive results, bacteria for 36.0%, and parasites for 5.3%. Our study underlines a dominant role of norovirus and toxigenic C. difficile as etiologic agents of acute gastroenteritis among the patients of general practitioners.

We examined the prognostic value of free malignant cells in the peritoneal cavity of patients with colon adenocarcinoma. In 1996-1999, 88 patients underwent peritoneal washing with cytologic analysis immediately before elective colon resection for adenocarcinoma with no evidence of peritoneal metastases. Peritoneal washing fluid was collected before abdominal exploration centrifuged immediately and stained with the May-Grünwald-Giemsa and Harris-Shorr methods. Malignancy was defined as recommended by Papanicolaou. Free malignant cells in peritoneal fluid were found in 25 of 88 (28%) patients (Dukes A 0, of 11, Dukes B 10 of 31, Dukes C 11 of 37, Dukes D 4 of 9). The positive rate was 24 of 75 (32%) among patients with tumors involving the serous layer and 1 of 13 (8%) among the others (p = 0.00989). Positive peritoneal washing was not significantly associated with survival in multivariate analysis.The presence of free malignant cells in the peritoneal cavity of patients with colon cancer provided no further prognostic information relative to the Dukes classification in this study. The 5 years survival rates were 48% among patients with positive and negative peritoneal washing respectively (p = 0.09).

Some WHO grade I intracranial meningiomas resected from the same sites and with the same quality of resection (Simpson's grading scale) recur, while others do not. The reasons for this variability in occurrence of recurrence have not yet been determined. We therefore investigated the prognostic recurrence value of seven biological markers on a series of completely resected WHO grade I meningiomas. For this purpose, we analysed a series of 33 WHO grade I meningiomas totally resected between 1980 and 1990 (a follow-up of 10 years), including 14 cases of recurrence. The fixed tumour material from each meningioma was submitted to histochemical analyses targeting galectin-3 and its binding sites, the S100A5, S100A6 and S100B proteins, and cathepsin-B and -D. The levels of expression were assessed semi-quantitatively (in terms of the staining intensity and the labelling index) and submitted to uni- and multivariate analyses. Of all the markers investigated, only S100A5 expression can be associated with any significant prognostic value in the matter of recurrence. More particularly, the meningiomas with high levels of S100A5 staining intensity either did not recur, or recurred later than those with a low immunopositive S100A5 intensity (P = 0.004). Cox regression analyses demonstrated that this latter marker was associated with significant prognostic values independent of the patients' ages. Furthermore, the combination of the patients' ages and S100A5 staining intensity permitted the identification of a group with a particularly high risk of recurrence, that is, the patients younger than 55 and with meningiomas exhibiting low S100A5 intensities (P = 0.001). In conclusion, the S100A5 protein could play a role in the recurrence of totally resected WHO grade I meningiomas.

CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the expression of glycan and glycan-binding sites in the wall of vessels taken from five such subjects (vs. five control subjects matched for age and sex). Specimens were taken from the brain, heart, kidney, liver and lung. Although the main vessel lesions were observed in the tissues depending on the blood-brain barrier, alterations to systemic vessels were also observed despite the absence of any symptoms. The histochemical expression of a panel of 10 biotinylated neoglycoconjugates [Gal-beta(1-4)-D-Glc, Galbeta(1-3)GalNAc, alpha-D-GalNAc, beta-D-GalNAc, GalNAcalpha(1-3)-D-GalNAcalpha, GalNAcalpha(1-3)-D-GalNAcbeta, beta-D-Glc, alpha-D-Man, l-Fucose and D-Glcalpha(1-4)-D-Glc], eight plant lectins (PNA, MAA, SNA, DBA, WGA, ConA, GNA and UEA-1) and two antigalectin antibodies was monitored by means of semiquantitative and quantitative computer-assisted microscopy. The data show the altered histochemical binding of plant lectins, such as UEA-1 and ConA, in the vessel walls of CADASIL subjects. The present work, based upon staining by a panel of neoglycoconjugates, provides a biochemical characterization of the alteration of vessel walls in the brain compared to other organs including the heart, kidney, lung and liver in CADASIL as opposed to control subjects. These glycohistochemical results suggest a functional relevance of protein-carbohydrate interactions in this disease.

To investigate whether epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas express S100 proteins differentially by immunohistochemical assaying the presence of S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B.Immunopositivity/negativity was recorded for each S100 protein in a series of 52 cases consisting of 12 epidermoid cysts, 12 branchial cysts, 15 adamantinomatous craniopharyngiomas and 13 acquired cholesteatomas. Except in the case of the craniopharyngiomas, immunoreactivity was assessed independently in the basal membrane and the basal, the internal and the keratin layers. Our data show that in contrast to S100B, which was rarely expressed, S100A1, S100A2, S100A4 and S100A5 were often present in these four types of epithelial lesions. S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed. These three proteins are expressed more often in craniopharyngiomas and cholesteatomas, the two more aggressive types of lesions.This is the first study to report data on the expression of seven S100 proteins in different histopathological groups of epithelial head and neck lesions, whose precise embryological origins are still a matter of debate. S100 proteins could possibly be used as markers to target this embryonic origin, since our results show that S100A3 and S100A6 (and, to a lesser extent, S100A5) are expressed differentially across these different groups of epithelial lesions.

In the present study we used computer-assisted microscopy to analyze the morphology of Feulgen-stained cell nuclei in cell populations obtained at the same time as routinely performed cervical smears and in the same way. We investigated in a series of 110 cases whether the quantitative morphonuclear description of cytological cervical samples is able to aid pathologists to distinguish between benign and more suspect premalignant lesions. For this task nuclear DNA content, nuclear morphometry (size and anisonucleosis level) and chromatin pattern-related parameters were compiled for each specimen enrolled in the database. A set of 32 normal and 17 high-grade squamous intraepithelial lesion (HSIL) specimens (with diagnostic confirmations) were selected as references and used to establish a discriminant model on the basis of cytometry-generated variables. This model was then used to score the remaining 61 cases in our series (including cases exhibiting benign cellular changes, squamous cells of undetermined significance, low-grade SIL and cancers). The results show that a model discriminating efficiently between normal and HSIL groups can be obtained by combining 5 quantitative features (1 DNA ploidy-related, 2 morphometrical and 2 chromatin texture features). A 97% specificity and an 88% sensitivity characterized the boundary so established. When applied to new cases, the model was in fact able to correct diagnoses for cases which had been down- or up-graded on the basis of the Bethesda system, and provided scores in accordance with histological control.

Regulation of adrenal corticosteroid secretion by leptin may involve interactions at multiple levels of the hypothalamic-pituitary-adrenal axis. To investigate the possible direct effects of leptin on corticosteroid secretion of human adrenocortical adenomas, cells from adrenocortical adenomas causing primary aldosteronism (n = 1) and Cushing's syndrome (n = 1), as well as cells from nonhyperfunctioning adrenocortical adenomas (n = 5) were isolated and incubated for 2 h with human recombinant leptin (1-1000 ng/ml) in the presence and absence of adrenocorticotrop hormone (ACTH), then cortisol, corticosterone and aldosterone concentrations in incubating media were determined using radioimmunoassays. It was found that leptin effectively and dose-dependently inhibited basal and ACTH-stimulated cortisol and corticosterone secretion in the three types of human adrenocortical adenoma cells. The inhibiting effect of basal corticosterone secretion was detectable in the presence of leptin concentration as low as 1 ng/ml, with decreases of corticosterone secretion to 34+/-4%, 57+/-11% and 79+/-9% in Cushing's syndrome, primary aldosteronism, and nonhyperfunctioning adrenocortical adenoma cells, respectively. The inhibition of basal cortisol secretion in the presence of low concentration of leptin was less prominent, but 10 ng/ml leptin significantly diminished basal cortisol secretion to 81+/-9% in adrenocortical adenoma cells from Cushing's syndrome, to 68+/-6% in adenoma cells from primary aldosteronism, and to 83+/-8% in cells from nonhyperfunctioning adenomas. The inhibition of ACTH-stimulated cortisol and corticosterone secretion by leptin was similar to those found in cells without ACTH stimulation. By contrast, leptin even at 1000 ng/ml concentration exerted no clear effect on basal and ACTH-stimulated aldosterone secretion in cells from primary aldosteronism and in those nonhyperfunctioning adenoma cells in which aldosterone secretion was detectable. These results indicate that leptin is a potent inhibitor of cortisol and corticosterone secretion in human adenomatous adrenocortical cells. The inhibition of these corticosteroids by leptin may represent a potentially important interaction that exists between leptin and the hypothalamic-pituitary-adrenal axis.

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9S100A5or =S100A4S100A12S100A6S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.

The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P0.001 to P0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.

Angiogenesis is the development of new blood vessels from the existing vascular bed. In normal conditions this tightly regulated process occurs only during embryonic development, the female reproductive cycle and wound repair. In contrast, in pathological conditions such as malignant growth, atherosclerosis and diabetic retinopathy, angiogenesis becomes persistent due to an imbalance in the interplay between the positive and negative regulatory signals controlling the process. Thus, the control of tumor neovascularization may lead to new therapeutic approaches. Indeed, several anti-angiogenic drugs are currently undergoing preclinical characterization and/or clinical investigation. Recent achievement has clarified the mechanisms of action leading to pathological angiogenesis and has highlighted the role of hypoxia, growth factors, growth factor-receptors, enzymes and cell adhesion molecules involved in the process. This knowledge has permitted the design of receptor antagonists, adhesion molecule blockers and new targeted vascular approaches including gene therapy.

The present study shows how an original mouse metastatic lung model was established from the MXT mammary adenocarcinoma. This metastatic model was obtained by injecting the C/MET clone into the tail veins of B6D2F1 mice. The C/MET clone corresponds to one of eleven cell clones that were isolated in vitro from the MXT model. Of these 11 clones, only the C/MET leads to lung metastatic tumor development when injected i.v. into mice. Furthermore, the C/MET clone colonizes the lung only. The present data show that the C/MET metastatic model and the MXT parental line are weakly (if reference is made to the P388 leukemia model) sensitive to adriamycin, clyclophosphamide and etoposide. However, under specific experimental conditions, the chemosensitivity of the C/MET model can be significantly increased. The C/MET model therefore appears to be an interesting pharmacological tool to test new investigational agents with anti-tumor potentialities to lung metastases.

Set up of an automatic image processing based method that enables the motility of in vitro aggregated cells to be evaluated for a number of hours.Our biological model included the PC-3 human prostate cancer cell line growing as a monolayer on the bottom of Falcon plastic dishes containing conventional culture media. Our equipment consisted of an incubator, an inverted phase contrast microscope, a Charge Coupled Device (CCD) video camera, and a computer equipped with an image processing software developed in our laboratory. This computer-assisted microscope analysis of aggregated cells enables global cluster motility to be evaluated. This analysis also enables the trajectory of each cell to be isolated and parametrized within a given cluster or, indeed, the trajectories of individual cells outside a cluster.The results show that motility inside a PC-3 cluster is not restricted to slight motion due to cluster expansion, but rather consists of a marked cell movement within the cluster.The proposed equipment enables in vitro aggregated cell motility to be studied. This method can, therefore, be used in pharmacological studies in order to select anti-motility related compounds. The compounds selected by the equipment described could then be tested in vivo as potential anti-metastatic.

Multiple endocrine neoplasia Type 2 (MEN2) is a hereditary tumour syndrome characterized by the association of medullary thyroid cancer, phaeochromocytoma and hyperparathyroidism. It is inherited as an autosomal dominant trait. During the past few years the cloning of the gene responsible for the syndrome, the ret protooncogene, made the molecular genetic diagnosis of the disease possible. In this study we demonstrate the results of the MEN2 mutation analysis performed in three members of a Hungarian MEN2A family. The mutation analysis was carried out according to the method of Dr. W. Hoppner's Laboratory (Hamburg) that is the main centre for MEN2 genetic diagnosis in Germany. Two Members of the family are affected, one suffered from both medullary thyroid cancer and phaeochromocytoma, the other (the first patient's daughter) had only medullary thyroid cancer. We found a ret exon 11 codon 634 mutation, that resulted in the change of TGC to TAC, a cysteine-tyrosine amino acid exchange. We found no mutation in the youngest member of the family. This result is of great clinical significance, because the carrier status of this individual can thus be excluded and, therefore, there is no need for prophylactic thyroidectomy and further clinical screening tests. As molecular genetic diagnosis of MEN2 becomes possible, the uncertain clinical examinations used for MEN2 diagnosis seems to be less important.