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Despite recent advances in the assessment, risk stratification, and treatment of acute pulmonary embolism (PE), it remains a leading cause of cardiovascular morbidity and mortality in the United States each year. Patient presentation and prognosis are heterogeneous, and a variety of diagnostic and therapeutic instruments have arisen to assist in providing patients with the appropriate level of care and aggressiveness of approach. Fortunately, a growing number of institutions now have pulmonary embolism response teams (PERT) that urgently assist with risk assessment and management of patients with massive and sub-massive PE. In service of providers at the point of contact with acute PE, this review aims to summarize the data pertinent to rapid risk assessment and the interpretation of diagnostics used to that end. The role of PERT and the indications for systemic fibrinolysis and invasive therapies are also discussed.

Radiation-induced coronary heart disease (RICHD) is the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin’s lymphoma and other prevalent mediastinal malignancies. The risk of RICHD increases with radiation dose. Exposed patients may present decades after treatment with manifestations ranging from asymptomatic myocardial perfusion defects to ostial, triple-vessel disease and sudden cardiac death. RICHD is insidious, with a long latency and a tendency to remain silent late into the disease course. Vessel involvement is often diffuse and is preferentially proximal. The pathophysiology is similar to that of accelerated atherosclerosis, characterised by the formation of inflammatory plaque with high collagen and fibrin content. The presence of conventional risk factors potentiates RICHD, and aggressive risk factor management should ideally be initiated prior to radiation therapy. Stress echocardiography is more sensitive and specific than myocardial perfusion imaging in the detection of RICHD, and CT coronary angiography shows promise in risk stratification. Coronary artery bypass grafting is associated with higher risks of graft failure, perioperative complications and all-cause mortality in patients with RICHD. In most cases, the use of drug-eluting stents is preferable to surgical intervention, bare metal stenting or balloon-angioplasty alone.

Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology.

Summary Background : Recently, biliary sludge has been strongly correlated with ‘idiopathic pancreatitis’. It is often diagnosed by trans-abdominal ultrasonography, despite the low sensitivity of this investigation. New scanners, using second harmonic imaging, may improve the quality of the echographic picture. Aim : To verify the impact of this methodology on the detection of biliary sludge in patients with ‘idiopathic’ pancreatitis. Methods : Fifty patients with ‘idiopathic’ pancreatitis observed over a 18-month period entered the study. Exclusion criteria were gall-bladder stones, polyps, clinical conditions related to biliary sludge development and haemolytic disorders. Patients were assessed blind by two operators using either conventional ultrasonography or second harmonic imaging. The parameters of diagnostic quality of both examinations were evaluated using, as the gold standard, microscopic examination of the gall-bladder content collected at endoscopy after cholecystokinin infusion. Results : An improvement in sensitivity, specificity, efficiency and negative predictive value was obtained by second harmonic imaging compared with conventional ultrasonography. Conclusions : Second harmonic imaging, in our experience, is a reliable non-invasive tool for the diagnosis and follow-up of biliary sludge in the course of ‘idiopathic’ pancreatitis.

Summary Background : Certain evidence suggests that Helicobacter pylori strains expressing genes for cytotoxin production show a higher sensitivity than non-cytotoxic organisms to eradication treatment. No data are available on the involvement of bacterium-related lesions in different therapeutic outcomes. Aims : (i) To investigate whether differences in eradication rates may be related to the different expression of virulent strains (cagA, vacA, iceA) in patients undergoing proton pump inhibitor-based triple therapy, and (ii) to evaluate whether therapeutic outcome may be affected by bacterium-induced gastric lesions. Methods : One hundred and ten H. pylori-positive subjects were enrolled. H. pylori was genotyped by polymerase chain reaction. Treatment consisted of lansoprazole–amoxicillin–clarithromycin, twice daily for 1 week. Eradication was checked by urea breath test. Results : The eradication rate was 70%, and the absence of cagA was associated with unsuccessful treatment. No difference between the groups with successful and unsuccessful eradication was found with regard to vacA and iceA. Lympho-epithelial lesions and fibrosis were associated with unsuccessful treatment. Conclusions : The present data confirm the importance of cagA (but not vacA and iceA) as a predictor of successful eradication. When fibrosis and lympho-epithelial lesions are present, therapy appears to be less effective. Therefore, these histological features may be involved in an unsuccessful therapeutic outcome.

Background and Aims. Transglutaminases are tissue enzymes involved in different neuronal processes including maintenance and signalling. However, their up-regulation elicited by a variety of noxae contributes to neurodegeneration. This study tested the hypothesis that experimental inflammation evoked transglutaminase up-regulation in myenteric neurons and that this event had an impact on neuronal survival. Methods. Rats with or without trinitro-benzene-sulphonic acid-induced colitis were used. One week after colitis induction, longitudinal muscle-myenteric plexus preparations were obtained from left colon to assess tissue-transglutaminase activity, protein and mRNA expression. Double labelling immunofluorescence using antibodies to neuron-specific enolase and transglutaminase was performed to identify myenteric neurons expressing transglutatninase. Additional sets of experiments evaluated the involvement of transglutaminase in the apoptotic process of cultured myenteric neurons. Results. Compared to controls, rats with colitis showed several tranglutaminase/neuron-specific enolase positive myenteric neurons. Western blot analysis and RT-PCR confirmed that in rats with colitis, the increased neuronal transglutaminase-immunoreactivity was associated with an increased enzyme expression. Similarly, transglutaminase activity was significantly higher than in controls (1100 +/- 280 mU/g vs. 725 +/- 119 mU/g, p

Background and aim: Meal-induced gastric distension and Cholecys- tokinin (CCK) are involved in the food intake. The relationship between meal gastric distension and CCK release have not been studied by non- invasive technique. We studied gastric volumes changes by Magnetic Resonance Imaging (MRI) and CCK serum levels after water preload and liquid (LM) and solid (SM) meals. Material and methods: Ten healthy subjects (4 F; Age 22 ± 3; BMI 23 ± 1) were studied on two days. Two test meals, a SM and LM with a similar nutrient composition (carbohydrate 46%; fat 32%; protein 22%) and energy content were used. Subjects were requested to ingest constant Kcal at 5 min interval (100 kcal/5 min) and to score their satiation level on a visual analogue scale graded 0–5 (1=threshold, 5= maximum satiation- MS). Experiment was scheduled as following: -10 min: 300 ml water preload (WPL); 0 min: solid or liquid meal until MS. CCK levels (ELISA, Phoenix, USA) were measured at baseline, after WPL, at 30, 60, 120 min of meal test. Gastric volume was evaluated by 1.5 T MRI at baseline, after water load, at MS and 120 min. Total (TGV) and proximal (PGV) gastric volumes (as difference respect to baseline) were manually traced by a trained observer. Data are presented as mean ± SD. Results: Kcal ingested and time to reach MS were significantly higher during SM (783 ± 244 kcal; 44 ± 14 min) than LM (630 ± 353 p < 0.01; 31 ± 17 p < 0.01). CCK serum peaks and time to peak were not different in LM and SM (1.62 ± 0.72 ng/ml vs 1.26 ± 0.87, and 41 ± 21 min vs 39 ± 14, respectively). TGV and PGV were not different between the two meal groups after WPL (SM: 271 ± 59 ml, 72 ± 46 vs LM: 309 ± 55, 74 ± 29) and at MS (SM: 554 ± 203 ml, 92 ± 32 vs LM: 560 ± 301, 132 ± 60). However TGV after WPL significantly correlated with CCK peaks in both meal groups (SM: r=0.73; p=0.016 and LM: r=0.62; p=0.049). PGV correlated with CCK peak in LM but not in SM (r=0.72, p=0.015; r=0.026, p=0.82). Conclusions: The MS induced by SM is not depending by GV and by CCK release. In contrast, the ability of LM to induce an earlier satiation is associated to the combined effect of the proximal stomach distension and the maximum CCK release. These results suggest a partial role of both total and proximal gastric distension in to determine CCK release. This relationship appears more evident with a liquid form of meal

Summary Background Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. Aim To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. Methods Thirty-two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full-dosage PPI therapy (esomeprazole 40 mg/day) was prescribed. Results In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P

Background and Aim: Colonic diverticulitis shows an high recurrence rate. Since no conclusive data are available about the optimal strategy in preventing diverticulitis recurrence, aim of our study was to assess three different therapeutic strategies in preventing diverticulitis recurrence Methods: 130 patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 Males, 49 Females, mean age 64.71 years, range 40-85) were prospectively assessed during a 2-year follow-up. After obtaining remission, the patients were treatedwithmesalazine 1.6 grams every day (59 patients, group A), or rifaximin 800 mg/day for 7 days every month (52 patients, group B), or did not take any therapy (19 patients, group C). Clinical, endoscopic and histological follow-up was performed after six, 12 and therefore every 12 months after diagnosis of AUD. Results: Fifty-four patients were excluded from final evaluation (see figure 1): 17 patients died; 21 were excluded due to taking unprescribed drugs during the scheduled treatment; 16 were lost to follow-up or were excluded because not compliant. Forty-four group A patients, 23 group B patients, 9 group C patients were available for the final assessment. Sustained remission was statistically higher in group A (93.18%) than group B (56.52%) and group C (44.44%) (A vs B: p=0.01; A vs C: p=0.03; B vs C: p=0.072). Persistence of endoscopic and histological damage were the only factors affecting diverticulitis recurrence. Conclusions: Patients taking mesalazine have lower risk of diverticulitis recurrence than patients taking rifaximin or taking no therapy, thanks to lower prevalence of persisting endoscopic and histological inflammation than in patients taking rifaximin or taking no therapy

Background and aim: Functional bowel disorders may follow acute intestinal infection. A single, retrospective study showed that a subset of dyspeptic patients had a history of gastroenteritis. No data are available in patients with prospectively identified postinfectious dyspepsia (PD). We aimed to characterize frequency, symptoms evolution and underlying mechanisms of functional dyspepsia after acute gastroenteritis. Material and methods: A total of 150 consecutive patients with undergoing acute gastroenteritis were screened and followed-up for 1 month (m). In patients with symptoms persistence upper GI endoscopy, breath test-based gastric emptying study and satiety testing (to estimate gastric fundus accommodation) were performed. Pattern and severity of symptoms were scored at 3, 6 and 12 m by standardized questionnaire. Gastric emptying and satiety testing were repeated at 6 m. Patients with previous diagnosis of FGIDs or organic disease were excluded. Normal values of gastric emptying rate and meal-induced satiety (120 min and 890 kcal, respectively) were obtained on 20 age/sex matched healthy subjects. Results: At baseline no signs of infection were found in the majority of the patients, except than giardia lamblia and salmonella tiphy in 3 and 1 patients. Persistence of dyspeptic symptoms at 1 m was observed in 31 subjects (18 male, age 28±10), with postprandial fullness, bloating, belching, nausea, epigastric pain, early satiety and vomiting being reported by 85, 70, 70, 56, 67, 48 and 19% of the patients, respectively; systematic analysis revealed that such pattern of symptoms was quite stable along the times. Although severity was gradually reducing for the majority of the symptoms, only patients reporting severe belching were significantly reduced at 12 m (70 vs. 12%, p

Background and aim: Antisecretory drugs for acid-related diseases are the second reimbursable group in the Italian Healthcare System. After the launching of generic lansoprazole (early 2006), several Ital- ian Regional Health Authorities have introduced rules to favour the prescription of less costly generic drugs. We aimed to evaluate the prescription of Proton Pump Inhibitors (PPIs) from Jan 2005 to Dec 2007 in a primary care setting. Material and methods: Analysis has been performed on a database of 100 medical practitioners that have managed an average of 144.000 inhabitants. Evaluations performed are the following: 1) PPI prescrip- tion (total and separately for Lansoprazole – L; Esomeprazole – E; Pantoprazole – P; Rabeprazole – R; and Omeprazole - O); 2) prevalence of the reimbursement purpose (Gastroprotection – G; Acid-Related Disease – ARD); 3) prevalence of patients with ARD categorized on the basis of PPI prescriptions as drugs box/year (1-3 short treatment – ST; 4-11 long treatment – LT; > 12 very long treatment – VLT). Data were expressed as Compound Annual Growth Rate (CAGR). Results: Patients with PPI prescriptions (at least one prescription) in the study population were 7188 (5.52%), 8972 (6.62%) and 10437 (7.40%) in 2005, 2006 and 2007, respectively. Total growth of PPI prescription in the three years expressed as CAGR was 16%, whereas the growth for each molecule was: L +66%; E +9%; P +8; R +4%; O -10%. The reimbursement purpose was significantly higher for G (CAGR +44%) than for ARD (CAGR +6%; p < 0.01). We found an increase of ARD patients with ST (2005: 3687; 2006: 4165; 2007: 4522), LT (2599, 2995, 3231) and VLT (2120, 2944, 3550) with a significant highest CAGR for VLT patients (ST +7.0%, LT +7.5%, VLT +18.7%; p < 0.01). PPI prescription showed a highest CAGR for L in VLT patients (78%), while the lowest one was for O in VLT patients (-14%). Conclusions: Generic PPIs has unexpectedly increased the prescrip- tion of whole drug class during the period 2005-2007. We observed a marked increase in a very long duration PPI treatment for ARD that caused a relevant resource consumption. Our data suggest that the appropriateness of PPI prescription after generic PPI introduction should be carefully monitored to distinguish between cost-effective from cost-ineffective PPI treatment

Publisher Summary This chapter discusses a study examining abnormal intestinal permeability to lactulose in patients with atopic dermatitis. Twenty patients (11 males and 9 females), aged 2–13 years, were studied. Diagnosis was based on standard clinical criteria. Ten healthy subjects (aged 3–12 years) were used as controls. History was negative for gastrointestinal and/or renal disorders, and also for exacerbation of eczema after ingestion of particular foods. The degree of activity of the disease was evaluated on the basis of skin signs and symptoms, and expressed in arbitrary units. The evaluation was always made by the same examiner. Clinical remission was obtained in all patients by standard treatment using topical preparations of corticosteroids and/or inert pastes. The results showed that serum IgE levels were elevated in 13 (65%) patients during the active phase of atopic dermatitis. The presence of circulating specific IgE antibodies was demonstrated by positive radioallergosorbent test in 11 (55%) patients, all of whom had antibodies against food allergens, in addition to those against inhalants and/or pollens.

This paper is adapted from a speech presented by Matilda Cuomo outlining the early parenting education program of the New York State Citizen's Task Force on Child Abuse and Neglect. Mrs. Cuomo co-chairs the Task Force with Cesar Perales, New York State's Commissioner for Social Services. The Task Force is comprised of 30 volunteers. All volunteers are professionals in the field of child care. Mrs. Cuomo also is honorary Chair of the New York State Council on Children and Families.

A 17-year-old female patient with features of epilepsy was treated with valproic acid. Two years later, hypoglycemia and hyperinsulinemia appeared. Transabdominal ultrasonography, spiral computed tomography, and indium-111 Octreoscan were performed without positive results. Endoscopic ultrasonography identified an oval tumor in the pancreatic tail with a color Doppler hypervascular pattern. Surgical enucleation decreased levels of insulin and C-peptide within 20 min, and the patient became free of symptoms and medications.

Helicobacter pylori (HP) related inflammation is mediated by tumour necrosis factor alpha (TNFalpha), which "in vitro" increases epithelial apoptosis in response to infection. In the early stages of HP gastritis, a raised epithelial apoptosis occurs; this phenomenon becomes less evident with progression towards intestinal metaplasia. Aim of our study was to analyze "in vivo" mucosal TNFalpha in relation to epithelial apoptosis in the progression of HP related histological damage. Antral biopsies from 20 HP positive patients were retrospectively studied: 10 with and 10 without intestinal metaplasia (IM and CG group respectively); samples of 10 dyspeptics with normal HP negative stomach (N) were used as control. The following parameters were evaluated by immunohistochemistry: 85 kDa caspase-cleaved fragment (p85) of human poly (ADP-ribose) polymerase (PARP) labelling index (LI) as marker of apoptosis and TNFalpha LI in stromal cells as marker of inflammatory response. Both epithelial apoptosis and mucosal TNFalpha expression were higher in chronic active gastritis compared to intestinal metaplasia and controls (PARP and TNFalpha LI: CG > IM > N; ANOVA & Student-Neumann-Keuls; p < 0.05 and p < 0.01, respectively). Pearson's coefficient showed a significant correlation between PARP and TNFalpha LI in IM and CG groups. Our data show that mucosal TNFalpha, similarly to what suggested "in vitro", may be related "in vivo" to epithelial apoptosis thus suggesting a possible mechanism for immune system involvement in the control of gastric epithelial turnover.

Despite the studies performed in the last 2 decades on oesophageal or gastrointestinal function and sleep parameters, we continue to have limited knowledge of how sleep interferes with gastrointestinal physiology. In general, pHmetry is used to monitor circadian gastro-oesophageal reflux activity, and 24-h analysis evaluates upright and supine position. The reflux activity recorded during upright periods is generally referred to as awake refluxes, while supine refluxes are considered nocturnal and related to sleep. From a clinical point of view, nocturnal heartburn is evaluated as a main sign of nighttime reflux, and the prevalence of such symptoms has been reported around 74% among patients suffering from chronic heartburn. Recent studies have shown the importance of nighttime gastro-oesophageal reflux in the development of oesophagitis and other extraoesophageal complications, and adenocarcinoma of the oesophagus. In a national population-based telephone interview survey of 1000 adults conducted in USA, 13% of the respondents reported experiencing heartburn only during nighttime, 20% reported heartburn during daytime only, while 65% of respondents experienced heartburn both day and night. Another important issue is the role of nighttime reflux events in the pathohgenesis of respiratory and aerodigestive tract diseases, such as pharyngitis, sinusitis, laryngitis, chronic bronchitis, and asthma, among patients with gastro-oesophageal reflux diseases (GORD). Supraoesophageal complications have not been systematically studied but great relevance has been given to the oesophageal clearance of nighttime reflux. Indeed, while upright refluxes (experienced during waking) tend to be short and to resolve quickly, supine refluxes (experienced during sleep) tend to be longer and to resolve more slowly. In addition the noxious effect of acid content on the tracheobronchial tree has been recently studied to evaluate upper oesophageal sphincter function during sleep. Indeed, this research shows that the pressure of this sphincter appears related to different phases of sleep, although it overall decreases during sleep. A relevant aspect is the negative influence of nighttime refluxes on sleep and, consequently, on most personal, occupational and social activities the following day. The socioeconomic consequence of these disturbances could be significant, which underlines the need for correct therapeutic strategies to deal with chronic nocturnal heartburn. This summary underlines some viewpoints regarding the studies made on GOR during sleep. However some questions do emerge from these studies. The aspects mentioned above mainly refer to a symptomatic nocturnal reflux; so the question that remain are: Which is the meaning of instrumentally recorded gastro-oesophageal refluxes alone? Are there differences between the refluxes recorded in the supine position during sleep or during awake periods? Can the discrimination between refluxes during wake and asleep states help the clinician better define the management of GORD? A study authored by Dickman et al. in this issue of Neurogastroenterology and Motility suggests that the principal characteristics of acid refluxes events in supine-awake periods resemble more closely those Address for correspondence Prof. Rosario Cuomo M.D. Gastroenterological Unit, Department of Clinical and Experimental Medicine, University of Naples ‘‘Federico II, Via Sergio Pansini 5, 80131 Naples, Italy. Tel. and fax: +39 0817463892; e-mail: rcuomo@unina.it Received: 5 July 2007 Accepted for publication: 10 July 2007 Neurogastroenterol Motil (2007) 19, 701–703 doi: 10.1111/j.1365-2982.2007.00993.x

OBJECTIVE: The effects of carbonated beverages on the gastrointestinal tract have been poorly investigated. Therefore, this study aims to assess the effect of carbonated water intake in patients with functional dyspepsia and constipation. METHODS: Twenty-one patients with dyspepsia and secondary constipation were randomized into two groups in a double-blind fashion. One group (10 subjects) drank carbonated water and the other (11 subjects) tap water for almost 15 days. Patients were evaluated for dyspepsia and constipation scores, and underwent a satiety test by a liquid meal, radionuclide gastric emptying, sonographic gallbladder emptying and colonic transit time, using radio-opaque markers. RESULTS: The dyspepsia score was significantly reduced with carbonated water (before = 7.9 +/- 2.8 after = 5.4 +/- 1.7; 0.05) and remained unmodified after tap water (9.7 +/- 5.3 9.9 +/- 4.0). The constipation score also decreased significantly ( 0.05) after carbonated water (16.0 +/- 3.9 12.1 +/- 4.4; 0.05) and was not significantly different with tap water (14.7 +/- 5.1 13.7 +/- 4.7). Satiety was significantly reduced with carbonated water (before = 447 +/- 146 kcal after = 590 +/- 245; 0.01). Gallbladder emptying (delta percent contraction) was significantly improved only with carbonated water (39.9 +/- 16.1% 53.6 +/- 16.7%; 0.01). CONCLUSION: In patients complaining of functional dyspepsia and constipation, carbonated water decreases satiety and improves dyspepsia, constipation and gallbladder emptying