Randomized clinical trial: a controlled pilot trial of the 5-HT4 receptor agonist revexepride in patients with symptoms suggestive of gastroparesis.

BACKGROUND: Gastroparesis is a chronic gastric disorder characterized by delayed gastric emptying without mechanical obstruction, and clinical symptoms as postprandial fullness, early satiety, bloating, nausea, vomiting, and abdominal pain. Prokinetic agents are used for the treatment of gastroparesis. Revexepride, a 5-hydroxytryptamine (serotonin) receptor (5-HT4 R) agonist, could be a good candidate drug for the gastroparesis treatment. AIM: In the current phase II, exploratory, double-blind, randomized, stratified, placebo-controlled, repeated dose trial (EudraCT number 2007-004997-23), the efficacy on gastrointestinal symptoms and gastric emptying rate, safety, and pharmacokinetic profile of three oral doses of revexepride (0.02, 0.1, and 0.5 mg administered orally t.i.d. for 4 weeks) was evaluated in trial participants (diabetic and non-diabetic) with upper gastrointestinal tract symptoms suggestive for gastroparesis. METHODS: Eighty participants, enrolled in four parallel treatment groups, were asked to score their symptom diary data, gastroparesis cardinal symptom index (GCSI), patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM), quality of life questionnaires, and meal-related symptom score. Gastric emptying rate was evaluated by (13) C-octanoic acid breath test. KEY RESULTS: The severity of the symptoms assessed by means of GCSI and PAGI-SYM decreased at Week 2 and decreased further at Week 4 in all treatment groups including placebo, with similar trends in all treatment groups. Quality of life improved in all treatment groups after 4 weeks of treatment. No differences on gastric emptying rate were shown between any of the active treatment groups and placebo. Revexepride was generally safe and well-tolerated. CONCLUSIONS & INFERENCES: Four weeks of revexepride treatment did not improve symptoms or gastric emptying over placebo in patients with symptoms suggestive of gastroparesis.

The P2X7 receptor is a key modulator of the PI3K/GSK3ß/VEGF signaling network: evidence in experimental neuroblastoma.

Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3ß/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3ß activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3ß, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.

Involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty rats with metabolic syndrome.

This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF) rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R). At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg) reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7%) and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health.

BACKGROUND: Menthol reduces intestinal motility in animal studies, an effect that is probably mediated by transient receptor potential channels. Peppermint oil (PO), with menthol as a major constituent, is widely used as a spasmolytic agent in irritable bowel syndrome. In the current study, we investigated the effect of acute PO administration on intragastric pressure (IGP) profiles and gastric sensorimotor functions in health. METHODS: Healthy volunteers underwent IGP measurement before and during continuous intragastric infusion of a nutrient drink (n = 13), and gastric barostat studies (n = 13). A single capsule of PO (182 mg) or placebo was administered during the studies in a randomized controlled crossover design. Throughout the studies, healthy volunteers scored 11 epigastric symptoms on a visual analogue scale (VAS); satiation was scored on a 6-point Likert scale during intragastric infusion. KEY RESULTS: During fasting, IGP and motility index (MI) of the proximal stomach decreased significantly after PO administration compared with placebo (P < 0.0001 and <0.05, respectively). In contrast, during intragastric infusion of the nutrient drink, no significant differences were detected between PO and placebo in IGP profiles, MI, satiation scores, and epigastric symptoms. The maximum infused volume, gastric compliance or sensitivity to balloon distention did not differ between both treatment arms. However, reduced appetite scores were seen during fasting after PO treatment, as compared with placebo (P = 0.01). Postprandial VAS scores were similar between PO and placebo. CONCLUSIONS & INFERENCES: Peppermint oil reduces IGP, proximal phasic contractility, and appetite, with negligible effects on gastric sensitivity, tone, accommodation, and nutrient tolerance in health.

A computed tomography-based comparative cephalometric analysis of the Italian craniofacial pattern through 2,700 years.

The aim of our study was to define the changes in morphovolumetric features of neurocranium, basicranium and splanchnocranium in the population of Campania, southern Italy, over the last 2,700 years. This was a very intense period for this region from both historical and evolutionary perspectives and was marked by the succession of colonisations, dominations and invasions by several European and non-European peoples, events that profoundly influenced the original genetic heritage, which subsequently became more complex. Unlike most previous authors, we based our craniometric comparative analysis on multidetector computed tomography (MDCT) studies of contemporary and ancient series dating to between the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks and measuring linear and angular indices through the use of multiplanar and tridimensional reformations. While highlighting a remarkable stability of 22/32 of the indices considered, as an effect of the role of the genetic heritage in preserving morphovolumetric features in a given population, statistical analysis showed some interesting results: the main changes concerned the splanchnocranium and the occlusion, indicating a higher sensitivity of these districts to environmental factors, mainly related to diet. Conversely, neurobasicranial complex morphovolumetric features remained amazingly intact. In particular, the neurocranium increased in overall capacity in response to the growing brain and changed shape with a progressive shift to a dolichocranic, flattened frontal pattern; the basicranium shape was preserved, as indicated by the stability of the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary, has undergone a dramatic involution, even conditioning gnathic structures with changes in palatal shape (more acute) and in the relationship between the jaws on the sagittal plane, resulting in increased prevalence of Angle's class I and III malocclusions.

Effect of the GLP-1 analog liraglutide on satiation and gastric sensorimotor function during nutrient-drink ingestion.

BACKGROUND/AIM: Liraglutide, a glucagon-like peptide-1 analog, induces weight loss. We investigated whether liraglutide affects gastric accommodation and satiation by measuring the intragastric pressure (IGP) during nutrient-drink consumption and using the barostat technique. METHODS: Ten healthy volunteers (HVs) were tested after placebo, 0.3, 0.6 or 1.2 mg liraglutide administration. IGP was studied during intragastric nutrient-drink (1.5 kcal ml(-1)) infusion (60 ml min(-1)), while the HVs scored their satiation on a graded scale until maximal satiation. In a separate session, isobaric distentions were performed using the barostat with stepwise increments of 2 mm Hg starting from minimal distending pressure, although HVs scored their perception; gastric volume was monitored 30 min before and until 60 min after ingestion of 200 ml of nutrient drink. Data are presented as mean±s.e.m. comparisons were performed with ANOVA (P<0.05 was significant). RESULTS: During nutrient-drink infusion, IGP decreased with 4.1±0.7, 3.0±0.4, 2.1±0.3 and 2.6±0.4 mm Hg (placebo, 0.3, 0.6 and 1.2 mg liraglutide, respectively; P<0.05). The maximum-tolerated volume was not different, except after treatment with 1.2 mg liraglutide (695±135 ml) compared with placebo (1008±197 ml; P<0.05); however, 1.2 mg liraglutide induced nausea in all volunteers. In the barostat study, liraglutide did not affect the perception or compliance, but significantly decreased gastric accommodation to the meal (168±27 vs 78.8±36.4 ml after treatment with placebo and 0.6 mg liraglutide, respectively; P<0.05). CONCLUSION: Although no effect on perception, compliance or satiation was observed, liraglutide inhibited gastric accommodation. Whether this effect is involved in the anorectic effect of liraglutide remains to be determined.

Review article: a comparison of glucagon-like peptides 1 and 2.

BACKGROUND: Recent advancements in understanding the roles and functions of glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting these peptides in therapeutic strategies. AIM: To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP-1 and GLP-2. METHODS: This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP-1 and GLP-2. RESULTS: Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit distinctive biological functions that are governed by the expression of their respective receptors, GLP-1R and GLP-2R. Through widespread expression in the pancreas, intestine, nervous tissue, et cetera, GLP-1Rs facilitates an incretin effect along with effects on appetite and satiety. GLP-1 analogues resistant to degradation by dipeptidyl peptidase-IV and inhibitors of dipeptidyl peptidase-IV have been developed to aid treatment of diabetes and obesity. The GLP-2R is expressed almost exclusively in the stomach and bowel. The most apparent role for GLP-2 is its promotion of growth and function of intestinal mucosa, which has been targeted for therapies that promote repair and adaptive growth. These are used as treatments for intestinal failure and related conditions. CONCLUSIONS: Our growing understanding of the biology and function of GLP-1, GLP-2 and corresponding receptors has fostered further discovery of fundamental biological function as well as new categories of potent therapeutic medicines.

Patients' survival in lung malignancies treated by microwave ablation: our experience on 56 patients.

OBJECTIVES: We retrospectively evaluated percutaneous CT-guided microwave (MW) ablation safety and efficacy in unresectable lung malignancies focusing on patients' survival. MATERIALS AND METHODS: All procedures were approved by the hospital ethical committee. From 2008 to 2012 we treated 69 unresectable lesions (44 lung cancer, 25 lung metastases) in 56 patients (35 men/21 women; mean age: 61.5 years). Treatment was performed under CT guidance using 14 G needles with a 3 cm active tip and a 55 W MW generator (Vivawave Microwave Coagulation System; Valley Lab). Treatment was performed at 45 W for 6-10 min. Patients were scheduled for a 3 and 6 month CT follow-up to evaluate lesion diameter and enhancement. Survival rate was evaluated by Kaplan-Meier analysis. RESULTS: Ablation procedures were completed according to protocol in all patients. Pneumothorax occurred in 18 patients and 8 required chest tube. Four lesions (all >4.3 cm) were retreated 20 days after the ablation because of peripheral focal areas of residual tumor. Follow-up CT evaluation showed a decrease in maximum diameter in 44/69 lesions (64%) and in 42/59 lesions (71%) at 3 and 6 months, respectively. In all cases no pathologic enhancement was observed. Cancer-specific mortality yielded a survival rate of 69% at 12 months, 54% at 24 months and 49% at 36 months, respectively. An estimate mean for survival time was 27.8 months with a standard error of 2.8 months (95% confidence interval: 22.4-33.2 months). CONCLUSION: Based on our experience, MW ablation seems to represent a potential safe and effective percutaneous technique in the treatment of lung malignancies. MW ablation may improve survival in patients not suitable to surgery.

[Craniofacial morphology and obstructive sleep apnoea-hypopnoea syndrome: a craniometric comparative analysis]. / Morfologia craniofacciale e sindrome delle apnee-ipopnee ostruttive nel sonno: un'analisi craniometrica comparativa.

PURPOSE: The aim of this study was to define the relationship between paediatric obstructive sleep apnoea-hypopnea syndrome (OSAHS) and craniofacial morphovolumetric features through comparative craniometric analyses between affected children and controls based on conventional cephalometry. MATERIALS AND METHODS: Cephalometric examinations of 40 children affected by OSAHS were retrospectively evaluated. Sixteen craniometric landmarks were identified, and 27 linear and angular indices related to craniofacial morphovolumetric features were measured. Subsequently, the same process of identifying landmarks and measuring indices was performed on the cephalometric examinations of 40 controls. For each index, we then calculated in both groups the mean, standard deviation, standard error and p value. By comparing the values obtained in the two series, we calculated the degree of significance of each difference between children with OSAHS and controls using the Student t test. RESULTS: Differences of only 5/27 linear and angular indices considered were not statistically significant between groups, thus confirming susceptibility to the disorder in relation to certain splanchnocranic morphovolumetric features. The most significant differences involved mandibular plane inclination and distance between landmark sella and hyoid bone, a reliable index being the vertical position of the latter. CONCLUSIONS: Despite the limitations associated with the 2D nature of conventional cephalometry, mainly related to projection and identification errors, and despite the upright position during examination, we consider the diagnostic value and information content of this technique high, thus reaffirming its role as a first-line imaging investigation in children with sleep-related breathing disorders.

Acute abdominal pain in childhood and adolescence: assessing the impact of sonography on diagnosis and treatment.

PURPOSE: To assess the impact of ultrasonography on defining the diagnostic and therapeutic pathways for pediatric patients admitted to the emergency department for acute abdominal pain. METHODS: We performed a retrospective study of all patients aged <16 years with acute abdominal pain who underwent ultrasound examination at our Diagnostic Imaging Department from October 2010 to March 2012. We investigated for each patient the pathway following ultrasound examination and definitive diagnosis. The impact of ultrasonography was defined based on the frequency with which the information resulting from this examination confirmed or denied the diagnostic suspicion made by the emergency physician on the basis of clinical and laboratory findings. RESULTS: In 497/729 patients (69 %), ultrasound examination did not determine variations in the diagnostic and therapeutic pathways, either because it confirmed the outcome of clinical examination and laboratory tests, or because, even addressing in the opposite direction to these, the emergency physician did not consider its result because of being particularly alarmed or sufficiently reassured by clinical examination and laboratory tests. In the remaining 232/729 cases (31 %), ultrasound examination determined an increase or a reduction of the provided care and attention (subsequently proved justified in the vast majority of cases) in spite of what was initially assessed based on clinical examination and laboratory tests. CONCLUSIONS: The results of our retrospective study demonstrated that ultrasonography was a valuable tool in the management of pediatric patients with acute abdominal pain together with clinical examination and laboratory tests.

Three-dimensional anal endosonography in depicting anal-canal anatomy.

PURPOSE: This report describes the advantages of 3D anal endosonography in depicting the normal anatomy of the anal canal in relation to sex and age. MATERIALS AND METHODS: A retrospective study was performed of 85 patients, 33 men and 52 women, previously examined with 3D anal ultrasound (US) for clinically suspected anorectal disease but found to be negative. The examinations were performed with a Bruel and Kjaer US system with a 2050 transducer, scanning from the anorectal junction to the subcutaneous portion of the external anal sphincter (EAS). The 3D reconstructions provided an estimation of sphincter length in the anterior and posterior planes, and axial 2D images enabled calculation of the thickness of the internal anal sphincter (IAS) and EAS in the anterior, posterior and lateral transverse planes. RESULTS: Distribution of the sphincter complex is asymmetric in both sexes: the EAS and IAS are significantly shorter in females, especially in the anterior longitudinal plane (p=0.005 and p<0.001, respectively). EAS and IAS thickness increases with age, especially the lateral IAS (R(2)=0.37, p<0.001) and the posterior EAS (R(2)=0.29, p=0.01). CONCLUSIONS: A good knowledge of anal-canal anatomy is essential to detect sphincter abnormalities when assessing pelvic floor dysfunction.

Role of Y(2) receptors in the regulation of gastric tone in rats.

We set out to determine the effect of peptide YY(3-36) (PYY(3-36)) on the gastric muscle tone in conscious rats by measuring intragastric pressure (IGP) during intragastric nutrient drink infusion. After an overnight fast, a chronically implanted gastric fistula was connected to a custom-made nutrient drink infusion system and a catheter to measure IGP. IGP was measured before and during the infusion of a nutrient drink (Nutridrink; 0.5 ml/min) until 10 ml was infused. Rats were treated with PYY(3-36) (0, 33, and 100 pmol·kg(-1)·min(-1)) in combination with a subcutaneous injection of the Y(2) receptor antagonists JNJ31020028 (10 mg/kg) or BIIE0246 (2 mg/kg). Experiments were also performed after subdiaphragmatic vagotomy and after pretreatment with 3 ml of nutrient drink (to mimic a fed state). IGP was compared as the average IGP during nutrient infusion, represented as means ± SE and compared using ANOVA. PYY(3-36) dose dependently increased the IGP during nutrient infusion (4.7 ± 0.3, 5.7 ± 0.5 and 7.3 ± 0.7 mmHg; P < 0.01) while JNJ31020028 and BIIE0246 could block this increase [4.4 ± 0.5 (P < 0.001) and 4.8 ± 0.4 (P < 0.05) mmHg, respectively]. Also in vagotomized rats, PYY(3-36) was able to significantly increase the IGP during, an effect attenuated by JNJ31020028. BIIE0246 and JNJ31020028 were not able to decrease the IGP when no PYY(3-36) was administered. PYY(3-36) increased gastric tone through an Y(2) receptor-mediated mechanism that does not involve the vagus nerve. Y(2) receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY(3-36), indicating that Y(2) receptors do not play a crucial role in the determination of gastric tone in physiological conditions.

GLP-2 receptor expression in excitatory and inhibitory enteric neurons and its role in mouse duodenum contractility.

BACKGROUND: Glucagon-like peptide 2 (GLP-2), a nutrient-responsive hormone, exerts various actions in the gastrointestinal tract that are mediated by a G-protein coupled receptor called GLP-2R. A little information is available on GLP-2R expression in enteric neurons and nothing on the interstitial cells of Cajal (ICC). METHODS: We investigated presence and distribution of the GLP-2R in the mouse duodenum by immunohistochemistry and the potential motor effects of GLP-2 on the spontaneous and neurally evoked mechanical activity. KEY RESULTS: The GLP-2R was expressed by the myenteric and submucosal neurons. Labelling was also present in nerve varicosities within the circular muscular layer and at the deep muscular plexus (DMP). No immunoreactive nerve fiber was seen within the longitudinal muscle layer. The GLP-2R-positive neurons were either excitatory (SP- and choline-acetyltransferase-positive) or inhibitory (vasoactive intestinal polypeptide and nNOS-positive). The ICC, both at the myenteric plexus and at the DMP, never expressed GLP-2R but, especially those at the DMP, were surrounded by GLP-2R-positive nerve varicosities co-expressing either excitatory or inhibitory neurotransmitters. Quantitative analysis demonstrated a consistent prevalence of GLP-2R on the excitatory pathways. In agreement, the functional results showed that the administration of GLP-2 in vitro caused decrease of the spontaneous contractions mediated by nitric oxide release and reduction of the evoked cholinergic contractions. CONCLUSIONS & INFERENCES: The present findings indicate that the GLP-2R is expressed by inhibitory and excitatory neurons, the GLP-2 inhibits the muscle contractility likely decreasing cholinergic neurotransmission and increasing nitric oxide production, and this effect is possibly mediated by the ICC-DMP recruitment.

Pathophysiological premises to radiotracers for bone metastases.

Aim of our paper is to review the most important radio-compounds that can be successfully used to detect and/or characterize bone metastases. From a didactic point of view, we made a distinction between two main categories , the first allowing to individuate bone's reaction (osteotropic agents), the second trying to detect metastatic tumor cells (oncotropic agents). A wide description of the most diffuse Tc-99m diphosphonates , including analysis of uptake mechanisms and pharmacokinetics, is followed by a brief report on pathophysiological premises to the clinical use of F-18 fluoride and of specific (radioiodine, radiolabeled somatostatin or cathecolamine analogues) or non specific, as Tc-99m sestamibi, F-18 fluorodeoxhyglucose, F-18 choline, F-18 thymidine) oncotropic agents. At the end, the possibility to use diagnostic radiotracers to act both in recruiting patients with bone metastases undergoing radionuclide therapy and for their dosimetric evaluation is also discussed.

Daily motor performance after switching levodopa to melevodopa: an open-label on advanced Parkinson's disease with "delayed-on" and/or"wearing-off".

AIM: Aim of the present study was to evaluate the clinical efficacy, tolerability and quality-of-life measures to melevodopa in advanced Parkinson's disease (PD) with motor fluctuations (MFs). METHODS: A total of 37 patients with advanced PD and MFs participated in the study. Patients were switched from standard l-dopa/carbidopa to melevodopa and were treated for 10 weeks. RESULTS: Assessment of "On-Day" time demonstrated improvement to about 0.7 hour in the melevodopa treatment. The benefit was greater in patients with "delayed-on" (P=0.002) and especially in those with both "delayed-on" and "wearing-off" (P<0.001). Most patients showed a significant improvement in PDQ-39 total score (P=0.002) and PSI distress domain (P<0.001). Instead, not significant difference was observed in patients with only wearing-off. CONCLUSION: These data show that melevodopa is an effective agent for improving daily motor performance and quality-of-life in PD with "delayed-on", also in association with "wearing-off".

Less frequent requests for In-111 pentreotide and its brothers of endocrinological interest.

The somatostatin receptor scintigraphy (SRS), using octreotide radiolabelled with 111In (octreoscan, OCTs), is a consolidated diagnostic procedure in patients with neuroendocrine tumors. A higher accuracy has been demonstrated with single photon emission computed tomography-CT, while a further improvement has been obtained with positron emission tomography (PET)-CT, using somatostatin analogues radiolabeled with 68Ga, significantly increasing the number of detected lesions. Although the well-known presence of an OCTs uptake in many benign diseases, when in an active phase, the application of SRS in these patients did not find any clinical relevance yet. In this paper we discuss two fields of endocrinological interest where SRS could play a clinical role. In patients with Graves exophtalmos, the capability to differentiate between active and non-active disease can be helpful in define prognosis and therapeutic strategies. In patients with endocrine paraneoplastic syndromes (PNS), SRS can help in finding the underlying neoplasm, contributing to its characterization as premise to a therapeutic choice. The possible role of a surgery guided by OCTs is also explained and suggested. The incremental value of PET-CT with Ga-68 peptides is hypothesized to reduce the number of unknown neoplastic lesions frequently present in patients with PNS.

Seven-Tesla micro-MRI in early detection of acute arterial ischaemia: evolution of findings in an in vivo rat model.

PURPOSE: Acute mesenteric ischaemia (AMI) is a life-threatening vascular emergency with a high mortality rate. Early diagnosis is the key to reducing its mortality rate and improving the quality of life. Although computed tomography (CT) is still the gold standard for acute intestinal disorders, over the last few years, magnetic resonance imaging (MRI) has become a useful alternative tool. An animal model of AMI was developed in order to study the effectiveness of MRI in early detection of this condition and to observe lesion evolution. METHODS: Thirty Sprague Dawley rats were randomly divided into two groups (n=15): in the first group, after laparotomy, the animals underwent ligation of the superior mesenteric artery (SMA), followed by macroscopic monitoring and histological evaluation; in the second, ischaemia was induced by squeezing a loop around the SMA 3 days before evaluation with 7-T micro-MRI. RESULTS: Macroscopically, a reflex spastic ileus followed by reflex hypotonic ileus and colour changes in some of the loops were detected. MRI evidenced luminal dilatation with air-fluid levels, free intraperitoneal fluid and bowelwall oedema. Histological analysis confirmed ischaemia and earlier damage involving the central portion of the ileum. CONCLUSIONS: This model shows the correct sequence of events during arterial AMI and demonstrates that MRI can be recommended for early diagnosis of these lesions.

Differential diagnosis between fibroadenoma, giant fibroadenoma and phyllodes tumour: sonographic features and core needle biopsy.

PURPOSE: The aim of this study was to analyse mammographic and ultrasound (US) features of fibroadenoma and phyllodes tumour and assess the diagnostic accuracy of mammography, US and US-guided core needle biopsy (CNB) in the differential diagnosis of these two lesions. MATERIALS AND METHODS: The results of the pathological analysis of excision biopsy of 83 lesions (67 fibroadenomas and 16 phyllodes tumours) were correlated with the findings of mammography, US and US-guided CNB performed on 83 women with a mean age of 45.4 years (range 18-75 years). RESULTS: Sensitivity, specificity and positive predictive values compared with histology were 45%, 50% and 79% for mammography, 34%, 69% and 82% for US and 81%, 97% and 87% for US-guided CNB (p=0.001). CONCLUSIONS: The almost complete overlap between mammographic and US parameters of fibroadenomas and phyllodes tumours and the absence of pathognomonic features preclude the differential diagnosis between the two histological types. US-guided CNB is a valuable tool in the differential diagnosis between fibroadenoma and phyllodes tumour.

Influenza A virus: radiological and clinical findings of patients hospitalised for pandemic H1N1 influenza.

PURPOSE: This paper describes the radiological and clinical findings identified in a group of patients with H1N1 influenza. MATERIALS AND METHODS: Between May and mid-November 2009, 3,649 patients with suspected H1N1 influenza presented to our hospital. Our study population comprised 167 (91 male, 76 female patients, age range 11 months to 82 years; mean age 29 years) out of 1,896 patients with throat swab positive for H1N1 and clinical and laboratory findings indicative of viral influenza. All 167 patients were studied by chest X-ray (CXR), and 20 patients with positive CXR and worsening clinical condition also underwent computed tomography (CT). The following findings were evaluated on both modalities: interstitial reticulation (IR), nodules (N), ground-glass opacities (GGO), consolidations (CONS), bacterial superinfection and pulmonary complications. RESULTS: Ninety of 167 patients had positive CXR results. Abnormalities identified on CXR, variously combined and distributed, were as follows: 53 IR, 5 N, 13 GGO, 50 CONS; the predominant combination was represented by six GGO with CONS. Of the 20 CXR-positive cases also studied by CT, 17 showed pathological findings. The abnormalities identified on CT, variously combined and distributed, were as follows: 14 IR, 2 N, 5 GGO; the predominant combination was 10 GGO with CONS. Despite the differences between the two modalities, the principle radiological findings of bacterial superinfection were tree-in-bud pattern, consolidation with air bronchogram, and pleural and pericardial effusion. Fifteen of the 20 patients studied by both CXR and chest CT showed respiratory complications with bilateral and diffuse CONS on CXR and CT. Six of 15 died: 4/6 of acute respiratory distress syndrome and 2/6 of multiple organ failure. CONCLUSIONS: Our study describes the radiological and clinical characteristics of a large population of patients affected by H1N1 influenza. CXR and chest CT identified the site and extent of the pulmonary lesions and documented signs of bacterial superinfection and pulmonary complications.