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RUNX1 (AML1, CBFalpha2, PEBP2alphaB) is a transcription factor essential for the establishment of the hematopoietic stem cell. It is generally thought that RUNX1 exists as a monomer that regulates hematopoietic differentiation by interacting with tissue-specific factors and its DNA consensus through its N terminus. RUNX1 is frequently altered in human leukemia by gene fusions or point mutations. In general, these alterations do not affect the N terminus of the protein, and it is unclear how they consistently lead to hematopoietic transformation and leukemia. Here we report that RUNX1 homodimerizes through a mechanism involving C terminus-C terminus interaction. This RUNX1-RUNX1 interaction regulates the activity of the protein in reporter gene assays and modulates its ability to induce hematopoietic differentiation of hematopoietic cell lines. The promoters of genes regulated by RUNX1 often contain multiple RUNX1 binding sites. This arrangement suggests that RUNX1 could homodimerize to bring and hold together distant chromatin sites and factors and that if the dimerization region is removed by gene fusions or is altered by point mutations, as observed in leukemia, the ability of RUNX1 to regulate differentiation could be impaired.

Background Left ventricular hypertrophy (LVH) is an independent and powerful risk factor for cardiovascular events and death. Serum uric acid (SUA) may induce LVH, on one hand, through an inflammatory effect which promotes cardiac hypertrophy and, on the other, through an activation of the renin-angiotensin-aldosterone system which generates hypertrophy and hyperplasia of myocytes and fibrosis of the heart Objectives Aim of the study was to investigate the correlation between SUA levels and left ventricular mass in a group of hypertensive patients Methods We evaluated 51 patients (mean age 74±10 years; range 49-87, F 37.7%; M 62.3%) with essential hypertension. Each patient underwent a standardized medical history and clinical examination, laboratory tests and echocardiographic assessment with the determination of left ventricular mass index (LVMI) Results Mean value of SUA was 6.68±2 mg/dl. Mean blood pressure (MAP) was 95±12 mmHg. A positive significant correlation between SUA and LVMI (P=0.029) was observed. After adjusting for MAP and age in standard multiple linear regression analysis, SUA level remains independently associated with LVMI suggesting that increased urate levels are associated with a higher myocardial mass. Conclusions Our results demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH could be a powerful predictor of cardiovascular events References Yoshio Iwashima, Takeshi Horio, Kei Kamide, Hiromi Rakugi, Toshio Ogihara and Yuhei Uric Acid, Left Ventricular Mass Index, and Risk of Cardiovascular Disease in Essential Hypertension. Hypertension 2006;47:195-202; Ayako Yoshimura, Hisashi Adachi, Yuji Hirai, Mika Enomoto, Ako Fukami, Eita Kumagai, Kyoko Ohbu, Sachiko Nakamura, Aya Obuchi, Yume Nohara, Tsutomu Imaizumi. Serum Uric Acid Is Associated With the Left Ventricular Mass Index in Males of a General Population. Int Heart J, January 2014 Cristiana Catena, GianLuca Colussi, Frine Capobianco, Gabriele Brosolo and Leonardo A. Sechi. Uricaemia and left ventricular mass in hypertensive patients. Eur J Clin Invest 2014;44(10):972-981 Disclosure of Interest None declared

The life cycle and seasonal distribution of a tropical population of Eneoptera surinamensis (De Geer, 1773) were analyzed aiming to verify whether this species life cycle is associated to the wet and dry seasons. The population studied was found at the Seasonal Alluvial Semi-deciduous Forest, Foz de Iguaçu, PR, Brazil (25º27'54.9'' S; 54º34'27.9'' W), which presents mild mesothermal and super humid climate. Field observations were made at 20- to 24-day intervals, with the first observation occurring on April 30th, 2002 and the last on April 25th, 2003. It was verified that the studied species is univoltine and cyclic with regards to the dry and wet seasons, therefore being heterodynamic and surviving the dry season as adult. O ciclo de vida e a distribuição sazonal de uma população tropical de Eneoptera surinamensis (De Geer, 1773) foram analisados com o objetivo de verificar se o ciclo dessa espécie tem associação com as estações secas e úmidas. A população analisada encontra-se na Floresta Estacional Semidecidual Aluvial, Foz do Iguaçu, PR, Brasil (25º27'54.9'' S; 54º34'27.9'' W), a qual apresenta clima mesótermico brando superúmido sem seca. As observações em campo foram realizadas em intervalos de 20 a 24 dias, sendo que a primeira observação ocorreu no dia 30/04/2002 e a última em 25/04/2003. Verificou-se que a espécie estudada é univoltina e cíclica em relação às estações secas e úmidas, sendo dessa forma heterodinâmica, sobrevivendo à estação seca como adultos.

Our retrospective experience underscores the ability of Doppler echocardiography to detect the cardiotoxicity of chemotherapy (functional and pericardial abnormalities, heart involvement) and points out the need for an accurate echocardiographic follow-up of hematologic patients.

Electron transfer through the redox metalloprotein azurin immobilized on Au (111) by its disulphide bridge is studied by scanning tunneling microscopy (STM) in buffer solution and (for the first time) in air. STM analysis gives evidences of a stable and robust binding of the molecules in both cases. Bright spots, associated with azurin molecules, are clearly visible in STM images. The image contrast of adsorbed azurin is highly affected by the bias potential, with proteins visible only for some well-defined voltage values. This experimental demonstration of the possibility to induce tunneling through azurin in air could disclose very interesting perspectives for the development of protein-based hybrid nanodevices operating in non-liquid environments.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual wellbeing. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta 4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1,52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure.Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years).The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT3 and FT4 values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r2 = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively).Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

Photorefractive screening-photovoltaic solitons are observed in lithium niobate. Two-dimensional bright circular solitons are formed thanks to a strong static bias field, externally applied, opposite to the photovoltaic internal field. The dynamics of the soliton formation is monitored and compared to a time-dependent numerical model allowing determination of the photovoltaic field. Efficient single mode waveguides are shown to be memorized by the soliton beam for a long time.

This paper presents a study carried out to evaluate policy provisioning performance, by the COPS-PR protocol, in a policy based environment. First of all the prototypes developed are presented. These simulate the component behavior of the two lower layers of a policy based management system. Then the various measurements, done on the prototypes, are shown. All measures are carried out for several scenarios, described through the use of appropriate configuration policies, in an increasing complexity order. It is demonstrated that the architecture of COPS-PR is scalable, though the PDP can become a bottleneck.

The optical and electronic properties of zero-dimensional (OD) semiconductor heterostructures were intense investigation in the last few years. The interest for such nanostructures is mainly due to their application to opto-electronic devices and quantum computers. Semiconductor quantum dots (QDs) are also of particular interest for the study of basic quantum mechanical effects. Carriers in quantum dots are confined in three dimensions since their de Broglie wavelength is comparable to the dot size. This leads to energy quantization and to the formation of electronic shells which resemble those of natural atoms. For this reason, {QDs} are often referred to as "artificial atoms." The atomic-like properties of such systems can be fully exploited only through the complete control of the geometry (shape, size) and composition of the dots. The simultaneous knowledge of these parameters is necessary to engineer the wave functions and to exploit the dot properties in functional devices. This is a tremendous task, as it requires the refinement of growth methods and nanoscale structural, optical, and electrical characterizations at the forefront of the present technologies.

The Authors describe a cutaneous recurrence of a thyroid follicular cancer, immediately above the thyroid nodule, in a 76-year-old woman with advanced multiple myeloma, 8 mo after a fine-needle axpiration biopsy performed with 22-gauge needles. © 1994 Wiley-Liss, Inc.

To evaluate if chronic viral hepatitis may be a protective factor for atherosclerosis.Echo-doppler of the carotid and femoral arteries and the abdominal aorta was used to examine 48 patients with a histological diagnosis of chronic viral hepatitis (42 hepatitis C virus-related, 6 hepatitis B virus-related), with a low degree of activity and preserved hepatic function, and 50 controls matched for age, sex and exposure to the main risk factors of atherosclerosis.The prevalence of atherosclerosis in patients was clearly lower than in controls in all investigated sites, although the difference was statistically significant only for the carotid arteries. The percentage of patients with carotid atherosclerosis was 27% in patients with liver disease and 56% in controls (P0.005). Furthermore, and again at the carotid level, the patients with liver disease had fewer atheromatous lesions (16 plaques vs. 59; P0.001) than controls as well as a lower degree of vessel stenosis. None of the liver disease patients presented with vessel stenosis above 30% vs. 8% of control subjects.Chronic viral hepatitis may help prevent from atherosclerosis.

In 1999-2000 CSELT has started to analyse the feasibility to provision Telephony over IP (ToIP) services. ToIP is different from voice over IP, because it is intended as a carrier-class service, fully featured and with quality guarantees, to be offered to large number of users, either overlapping or substituting classical POTS services. The analysis has been both theoretical and experimental: first a model for quality of service evaluation has been developed, in order to cope with all the aspects that allow to characterise the ToIP service (voice quality, signalling quality, supplementary telephony services, OAMP these concepts have then been validated on a prototype system provided by a leading manufacturer. From our theoretical analysis and lab experiment we have seen that the architectures proposed in the standardisation bodies and by the manufacturers seem to be adequate for the provisioning of ToIP services. From a functional point of view, the system experimented, in particular considering its prototype nature, has given good results, in terms both of voice quality and of signalling quality. The big problem that remains to be resolved is the reliability of the systems, that is a fundamental concept for providing carrier-class services. The detailed results of both the theoretical analysis and the lab experiment are presented.

This paper describes the formation of glutamate dehydrogenase monolayers on silicon dioxide, and their characterization by means of physical techniques, i.e., fluorescence spectroscopy and Fourier-transform infrared spectroscopy. Detailed investigations of the intrinsic stability of native proteins in solution were carried out to elucidate the occurrence of conformational changes induced by the immobilization procedure. The enzyme monolayers were deposited on SiO2 after preexposing silicon surfaces to 3-aminopropyltriethoxysilane and reacting the silylated surfaces with glutaric dialdehyde. The optical characterization demonstrates that the immobilization does not interfere with the fold pattern of the native enzyme. In addition, fluorescence spectroscopy, thermal denaturation, and quenching studies performed on the enzyme in solution well describe the folding and unfolding properties of glutamate dehydrogenase. The photophysical studies reported here are relevant for nanobioelectronics applications requiring protein immobilization on a chip.

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

Background: Polycythemia vera (PV) is characterized by erythrocytosis, thrombocytosis, and/or leukocytosis and a broad range of disease-related symptoms. In high-risk patients, the most common first-line treatment is hydroxyurea (HU). The open-label RESPONSE trial demonstrated that ruxolitinib (RUX), a JAK1/JAK2 inhibitor, provided superior efficacy compared with best available therapy in patients with PV who were resistant to or intolerant of HU according to modified European LeukemiaNet (ELN) criteria. This study (RELIEF) was conducted in patients receiving a stable dose of HU and who were generally well controlled but reporting disease-associated symptoms, comparing the change in PV-related symptom burden in patients continuing their HU therapy with those switching to RUX treatment. Methods: RELIEF was a randomized, multicenter, double-blind, double-dummy, phase 3b study of patients with PV aged ≥18 years on a stable dose of HU monotherapy and reporting PV-related symptoms. Patients were required to be receiving HU for ≥12 weeks prior to enrollment and on the same dose level for the last 4 weeks, and have a score ≥8 on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) cytokine total symptom score (TSS-C). The TSS-C comprised symptoms of itching, tiredness, muscle ache, night sweats, and sweats while awake; each symptom was rated on a scale of 0=absent to 10=worst imaginable, with a maximum TSS-C score of 50. Patients also had to meet one of the following: ≤1 phlebotomy in the previous 6 months or no palpable splenomegaly. Those eligible were randomized 1:1 to receive RUX 10 mg BID and HU-placebo, or HU at the same dose/schedule and RUX-placebo. Dose adjustments were permitted for safety and efficacy. After Week 16, patients could receive open-label RUX until Week 48. The primary endpoint was the proportion of patients with a ≥50% reduction in TSS-C at Week 16; secondary endpoints included proportion of patients with a ≥50% reduction in individual TSS-C symptoms and safety. Results: Overall, 54 and 56 patients were randomized to RUX and HU, respectively; 87.0% and 89.3% remained on treatment through Week 16. At baseline, the median age (range) was 64 (36-87) in the RUX group and 66 (19-85) in the HU group; 44% and 61% were men. The majority of patients in the RUX and HU groups did not have baseline platelet counts or WBC above ELN thresholds: platelets >400 and ≤600 x 109/L (RUX 31.5%, HU 28.6%), >600 x 109/L (3.7%, 8.9%); WBC >10 and ≤15 x 109/L (16.7%, 16.1%), >15 x 109/L (11.1%, 14.3%). In the RUX and HU groups, the mean TSS-C at screening (22.4, 23.1) was higher than that at baseline (16.7, 18.0); the ratio of screening to baseline TSS-C was 1.7 and 1.6. The proportion of patients achieving a ≥50% reduction from baseline in TSS-C at Week 16 (primary endpoint) was 43.4% in the RUX group and 29.6% in the HU group (P=0.139; OR, 1.82; 95% CI, 0.82-4.04). The proportions of patients in the RUX vs HU groups achieving a ≥50% reduction in scores for itching and tiredness at Week 16 were 40.0% vs 26.4% and 54.2% vs 32.0%, respectively. Median percentage changes in individual TSS-C symptoms are shown in Table 1. Additional analyses found no correlation between individual changes in HU dose from baseline to Weeks 13-16 and percentage change in TSS-C in the HU arm (r2=0.030). Even patients maintaining the same HU dose from prior to study entry through Week 16 reported symptom improvement: 12/35 (34.3%) with no dose change, 4/12 (33.3%) with a dose increase, and 0/9 (0%) with a dose decrease had a ≥50% reduction in TSS-C. The most common nonhematologic adverse events in the RUX arm on randomized treatment were fatigue (20.4% RUX vs 10.7% HU), headache (16.7% vs 5.4%), and dizziness (13.0% vs 8.9%). The most common adverse events on HU were diarrhea (9.3% RUX vs 19.6% HU) and constipation (7.4% vs 12.5%); most events were grade 1 or 2. Grade 3 or 4 anemia or thrombocytopenia (lab values) were not reported in the RUX group; two patients in the RUX group had grade 3 or 4 neutropenia. Conclusion: In generally well controlled PV patients receiving a stable dose of HU, there was a positive trend in symptom improvement for patients switched to RUX therapy versus those continuing on HU therapy, although this was not statistically significant. The 34% response rate among patients who continued to receive a stable HU dose suggests a placebo effect that led to an underpowered study. Further analyses are required to better interpret these findings. Disclosures Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Yacoub:Alexion Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Membership on an entity's Board of Directors or advisory committees. Koschmieder:Novartis Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Byrne:Novartis Pharmaceuticals: Honoraria. Verstovsek:Incyte Corporation: Research Funding. Hunter:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. He:Incyte Corporation: Employment, Equity Ownership. Morozov:Novartis Pharmaceuticals: Employment, Equity Ownership.

Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve-mediated effect of specific NK1, NK2 and NK3 receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC).Cumulative concentrations of Sar9Met(O2)11 substance P (selective NK1 receptor agonist), [Ala5,beta-Ala8]-neurokinin A (4-10) (selective NK2 receptor agonist) and [MePhe7]-neurokinin B (selective NK3 receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off-contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0.5--10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated.In control preparations, the rank order of potency was: NK2 receptor-selective agonistNK3 receptor-selective agonistNK1 receptor-selective agonist. The off-contraction was found to be reduced by about 30--40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK1 receptor agonist did not modify the off-contraction measurements in either control or ICC preparations. Conversely, both NK2 and NK3 receptor agonists significantly (P0.01) increased the off-contraction in ICC preparations only. This increased response was fully antagonized by MEN-10627, a NK2 and NK3 receptor antagonist depending on the dose.We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.

Impaired gastrointestinal function outside the esophagus has been found in achalasic patients. Moreover, achalasia may occur in diseases in which a systemic dysautonomia is evident. These findings raise the question of whether a generalized subclinical alteration of autonomic control is also present in primary achalasia. Cardiovascular reflex tests and power spectral analysis of heart rate variability were studied in patients with primary achalasia to establish whether autonomic nervous system changes are present in districts other than the gastrointestinal tract. Nineteen normotensive patients with untreated primary achalasia and with no history of cardiac, renal, or endocrinological diseases were examined. Cardiovascular reflex tests included: the tilt test (10 min at 65 degrees), Valsalva maneuver (40 mm Hg for 15 sec), deep breathing (6 breaths/min), and sustained handgrip (30% of maximal effort for 5 min). The parameters evaluated were systolic and diastolic blood pressure (continuously recorded), ECG, oronasal and thoracic respiration, tachogram, and plethysmogram. To evaluate the balance between parasympathetic and sympathetic functions, power spectral analysis of the heart rate variability was carried out. Each patient was paired with two sex- and age-matched healthy controls. In achalasic patients the head-up tilt test, Valsalva maneuver, deep breathing test, and sustained handgrip did not show significant differences from the control group. Low-frequency (LF) and high-frequency (HF) spectral powers and the ratio of LF to HF did not differ in both groups. This study failed to disclose impaired cardiovascular autonomic control in achalasic patients. We suggest that in primary achalasia the defect is limited to the gastrointestinal tract.

Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects ('off contraction') of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC).Cumulative concentrations of erythromycin (1-20 microM) and motilin (0.05-1 microM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5-10 microM) and motilin (0.05-0.5 microM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1-5 Hz, 20 V, 1 msec pulse trains lasting 1 min).The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose-response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%).Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.

Liver metastases from differentiated thyroid tumors are unusual clinical findings, and are only rarely hyperfunctioning. We report a case of thyrotoxicosis caused by a huge and surgically unresectable liver metastasis from follicular thyroid cancer, unresponsive to treatment with large doses of thionamides. To avoid the hazardous side effects of (131)I treatment in a severely thyrotoxic patient, a preliminary debulking of the liver mass was performed by means of percutaneous interstitial laser photocoagulation. Three treatments (total energy delivery: 7200 J) were performed under ultrasound guidance, with no serious complications, during a 2-week period. One month later, serum thyroid hormones had decreased, general condition was improved, and magnetic resonance evaluation revealed large and well-defined areas of necrosis of metastatic tissue. During the following 10 months, the patient underwent 3 radioiodine treatments. Eighteen months after diagnosis, thyroid hormones were within normal levels, liver mass decreased, and the clinical condition markedly improved. The combination of percutaneous interstitial laser photocoagulation treatment and radioiodine therapy made possible the effective management of a hyperfunctioning and surgically untreatable liver metastasis from thyroid follicular carcinoma, avoiding the side effects of (131)I therapy in a thyrotoxic patient and increasing the effectiveness of radioiodine-induced neoplastic tissue ablation.

We performed chromosome microdissection in order to define the "de novo" rearrangement observed in a female patient affected by: frontal microgyria, mild psychomotor retardation, thoracic scoliosis, XIIth rib asymmetry and facial dysmorphisms. Through the use of the micro-FISH we evidenced a deletion of the 3p25pter region and a 4p16.1 duplication. We performed a karyotype-phenotype correlation in our patient and in the ones previously reported in literature which had a 3p25pter deletion or the 4p16 duplication.

The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.

MOS-B data corrected by standard calibration procedures are affected by striping in most channels. Striping arises because of the not perfect equalisation of the CCD array. The authors present a post-launch calibration method based on images of homogeneous targets. They focus on the results obtained on sea target images; such a case study is of great interest because it is related to ocean colour applications for which the MOS-B sensor was especially designed.

Summary To characterize 5-hydroxytryptamine (5-HT) receptors in rat perfused mesenteric vascular bed (MVB), the effect of 5-HT and related compounds was investigated by functional assay. In quiescent preparations, 5-HT elicited a concentration-dependent conctractile response. After addition of ketanserin, a 5-HT2 receptor antagonist, EC50 values were significantly higher than in controls. In noradrenaline (NA)-precontracted preparations, under continuous infusion of ketanserin, 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced relaxation. Their rank order of relaxant potency and maximum effect were sumatriptan > 5-HT > 5-CT. Methysergide (1 μM) and spiperone (20–100 nM) caused a rightward shift of the relaxation curve to sumatriptan. These data suggest that vasodilatation in rat MVB is mediated by an ‘atypical’ subtype of 5-HT1-like receptor, which reveals a pharmacological profile similar to that of the 5-HT1D receptor. The involvement of both 5-HT3 and 5-HT4 receptors can be ruled out, since tropisetron (up to 10 μM) was not able to antagonize the relaxant effect by sumatriptan. Under granisetron infusion (3 μM), the contractile response evoked by perivascular nervous stimulation, but not exogenous NA contraction, was significantly reduced (P < 0.001). These data demonstrate the presence of 5-HT3 receptors in peripheral neurones, modulating neurotransmitters release.