Extreme particle acceleration in the microquasar Cygnus X-3.

Super-massive black holes in active galaxies can accelerate particles to relativistic energies, producing jets with associated gamma-ray emission. Galactic 'microquasars', which are binary systems consisting of a neutron star or stellar-mass black hole accreting gas from a companion star, also produce relativistic jets, generally together with radio flares. Apart from an isolated event detected in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar, with the consequence that we are as yet unsure about the mechanism of jet energization. Here we report four gamma-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 (an exceptional X-ray binary that sporadically produces radio jets). There is a clear pattern of temporal correlations between the gamma-ray flares and transitional spectral states of the radio-frequency and X-ray emission. Particle acceleration occurred a few days before radio-jet ejections for two of the four flares, meaning that the process of jet formation implies the production of very energetic particles. In Cygnus X-3, particle energies during the flares can be thousands of times higher than during quiescent states.

Terrestrial gamma-ray flashes as powerful particle accelerators.

Strong electric discharges associated with thunderstorms can produce terrestrial gamma-ray flashes (TGFs), i.e., intense bursts of x rays and γ rays lasting a few milliseconds or less. We present in this Letter new TGF timing and spectral data based on the observations of the Italian Space Agency AGILE satellite. We determine that the TGF emission above 10 MeV has a significant power-law spectral component reaching energies up to 100 MeV. These results challenge TGF theoretical models based on runaway electron acceleration. The TGF discharge electric field accelerates particles over the large distances for which maximal voltages of hundreds of megavolts can be established. The combination of huge potentials and large electric fields in TGFs can efficiently accelerate particles in large numbers, and we reconsider here the photon spectrum and the neutron production by photonuclear reactions in the atmosphere.

Sonographic demonstration of a spontaneous rectus sheath hematoma following a sneeze: a case report and review of the literature.

Spontaneous rectus sheath hematoma (SRSH) is an uncommon cause of acute abdominal pain characterized by bleeding within the rectus sheath; it is a benign condition and, in most cases, it is treated conservatively. Bleeding of the abdominal wall is an unusual condition that is quite challenging to identify promptly and can be easily overlooked during a routine physical examination. In daily practice, anticoagulant therapy is one of the main risk factors for hemorrhagic events. In this respect, we report a rare case of spontaneous hematoma of the abdominal wall (diagnosed and monitored through an ultrasound examination) that arose after sneezing in a patient receiving anticoagulant treatment.

Not all abolished lung sliding are pneumothorax: the case of a particular lung atelectasis.

INTRODUCTION: Lung ultrasound (LUS) is expanding from the field of emergency medicine, also to the pneumological specialist field, becoming part of the diagnostic procedure of lung consolidation. CASE PRESENTATION: A 78-year-old male was admitted to our emergency department for exertional dyspnea. LUS was performed, thus showing at right hemitorax air interface, A lines pattern, pleural sliding abolished on the whole hemitorax, thus suggesting a pneumothorax, but no evidence of lung point. A scan of lower lung segment showed an absence of the diaphragmatic excursion, suggestive for hemiparalysis of the diaphragm muscle, then confirmed by a subcostal scan. Moreover, at the lower segment of right hemitorax there was mild pleural effusion allowing the visualization of a round-shaped parenchymal consolidation with the absence of air bronchograms. CONCLUSIONS: LUS allowed the visualization of a particular and rare disease such as anthracosis-associated rounded atelectasis, thus leading to a more correct and faster patient management.

Gallbladder polyps ultrasound: what the sonographer needs to know.

Gallbladder polyps are protuberances of the gallbladder wall projecting into the lumen. They are usually incidentally found during abdominal sonography or diagnosed on histopathology of a surgery specimen, with an estimated prevalence of up to 9.5% of patients. Gallbladder polyps are not mobile and do not demonstrate posterior acoustic shadowing; they may be sessile or pedunculated. Gallbladder polyps may be divided into pseudopolyps and true polyps. Pseudopolyps are benign and include cholesterolosis, cholesterinic polyps, inflammatory polyps, and localised adenomyomatosis. True gallbladder polyps can be benign or malignant. Benign polyps are most commonly adenomas, while malignant polyps are adenocarcinomas and metastases. There are also rare types of benign and malignant true gallbladder polyps, including mesenchymal tumours and lymphomas. Ultrasound is the first-choice imaging method for the diagnosis of gallbladder polyps, representing an indispensable tool for ensuring appropriate management. It enables limitation of secondary level investigations and avoidance of unnecessary cholecystectomies.

Gamma-ray localization of terrestrial gamma-ray flashes.

Terrestrial gamma-ray flashes (TGFs) are very short bursts of high-energy photons and electrons originating in Earth's atmosphere. We present here a localization study of TGFs carried out at gamma-ray energies above 20 MeV based on an innovative event selection method. We use the AGILE satellite Silicon Tracker data that for the first time have been correlated with TGFs detected by the AGILE Mini-Calorimeter. We detect 8 TGFs with gamma-ray photons of energies above 20 MeV localized by the AGILE gamma-ray imager with an accuracy of ∼5-10° at 50 MeV. Remarkably, all TGF-associated gamma rays are compatible with a terrestrial production site closer to the subsatellite point than 400 km. Considering that our gamma rays reach the AGILE satellite at 540 km altitude with limited scattering or attenuation, our measurements provide the first precise direct localization of TGFs from space.

Erectile dysfunction after therapy with metoprolol: the Hawthorne effect.

AIMS: It is often assumed that beta-blockers, e.g. metoprolol (METO), induce erectile dysfunction (ED) in men. However, cardiovascular diseases can also induce ED and there is also the possibility that psychological factors, such as fear of the disease and side effects of the prescribed drug, may also induce ED. Thus, it is often assumed that beta-blockers induce ED in a large percentage of men, but this statement is not well validated and the role of the pharmacologic effect of METO per se on the occurrence of ED is largely unknown. To get an answer we selected 114 men (age 57 +/- 4.7 years) without ED but with newly diagnosed arterial hypertension, and who could be treated with METO. METHODS: METO (100 mg/day) was given as a retard formulation. The hypertensive men were randomized into 3 groups. In group 1 patients were fully informed (they knew that the drug was METO and that it might induce ED). In group 2 patients were partially informed (they knew that the drug was METO, but were not informed that it might induce ED). In group 3 patients were not informed either about the drug used or about the possible occurrence of ED. The first phase of the study lasted 60 days. After 60 days the incidence of ED was 32% in group 1, 13% in group 2, and 8% in group 3 (p < 0.01). All patients with ED entered the second, cross-over, double-blind phase of the study. METO was continued at unchanged dosage, and tadalafil (20 mg) and a placebo were given to treat ED. RESULTS: Both treatments were equally effective. CONCLUSION: Prejudice about the possible occurrence, i.e. the Hawthorne effect, of ED with METO facilitates the occurrence of this side effect in hypertensive men. Since the etiology of this ED is largely psychological, it is not surprising that placebo is as effective as tadalafil in reversing this side effect.

Sharing knowledge is the key to success in a patient-physician relationship: how to produce a patient information leaflet on COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide, and its prevalence is rising. In Italy, respiratory diseases are the third most common cause of death. The aim of the study is to produce a patient information leaflet (PIL) designed to educate patients about COPD in accordance with the best recommendations based on evidence and guidelines for the production of good quality written information, and to evaluate the impact of this intervention on the patients' knowledge of COPD. METHODS: The study was conducted in the Department of Chest Diseases of the Cardarelli Hospital, Naples, Italy. A total of 166 patients admitted with a diagnosis of COPD participated in the study. Patients were asked to answer 10 multiple-choice questions compiled to assess their knowledge of the disease and then to read the leaflet. Two days later they were asked to complete the questionnaire again to assess their post-intervention knowledge. Analysis of the data was performed using SPSS version 15.0. RESULTS: After reading the leaflet, a statistically significant increase in the proportion of correct responses was noted (p < 0.001 by Wilcoxon signed rank test). Patients had retained the knowledge gained at the one year followup (p < 0.05 by Cochran's Q test). CONCLUSIONS: An educational intervention directed at adults with COPD had a positive impact on the patients' knowledge of COPD and this effect is long lasting.

Mantle cell lymphoma: from ultrasound examination to histological diagnosis.

We report the case of a 42-year-old patient referred to our department for the examination of two large, symmetrical inguinal lumps. The ultrasound examination of the swollen lymph node demonstrated a cortical echogenicity greater than the medullary echogenicity, and the vascularization stop around the cortical zone suggested a pathological pattern of mantle cell lymphoma. In this type of lymphoma, lymphocytes are localized in a mantle zone, inducing a thickening of the lumps. Therefore, for the first time, ultrasound examination detected sonographic vascular features of mantle cell lymphoma, allowing the identification of the disease and suggesting the specific histological diagnosis.

Stress-induced cardiomyopathy: A review.

In clinical practice it is essential to bear stress-induced cardiomyopathy (SICMP) in mind as it is an insufficiently known cardiac pathology that mimics acute coronary syndromes (ACS), often with signs of cardiac failure. In the chronic phase, it poses differential diagnostic problems with regard to coronary artery pathology. Taxonomic confusion, due to the pathology also being called "takotsubo" or "ampulla cardiomyopathy", has resulted in inappropriate diagnoses and therapy. Available evidence strongly suggests that, in the presence of several cardiac risk factors, excessive sympathetic stimulation may induce this cardiomyopathy. The predilection of this cardiomyopathy for Mediterranean and Indo-Asian women, who represent 85% of cases, is probably explained by the fact that there is a significant correlation between female gender, a short (<158 cm) stature, a small (<1.9 m(2)) body surface area, and hypoplastic coronary arteries. Furthermore, 40% of SICMP patients have a hypoplastic branching of the coronary arteries in the apical region of the heart. This anomaly strongly favors the apical localization of the dyskinesia. The prognosis of SICMP is good as far as life expectancy is concerned. However, in most cases, the symptoms become chronic, medical treatment rarely improves dyspnea and chest pain, and the quality of life is, therefore, reduced. In this paper, we address diagnostic misunderstandings and we review the clinical and pathophysiological features of SICMP.

Intrasubject between-day variability of PD20 methacholine assessed by the dosimeter inhalation test.

The intrasubject between-day variability of the methacholine inhalation test (MIT) was estimated in a group of 30 patients (15 males, mean age 29 yr), representative of a wide range of degrees of nonspecific bronchial responsiveness (from normal to severely increased). In each patient, an MIT with the dosimeter method was carried out on three separate occasions within one week, keeping as constant as possible both the technical and patient-related factors (FEV1 within +/- 5 percent, no recent airway inflammation) and independently from operator-related factors (three tests, three different operators blinded with regard to previous MIT results). On each occasion, twofold increasing doses of methacholine were given from 6.25 to 3,200 micrograms as cumulative doses, at five-minute intervals by means of a dosimeter Me.far MB3 (nebulization time 0.8 +/- 0.2s, output 5 +/- 0.2 microliters/puff). The FEV1 was measured initially and 1.5 and 3 minutes after each inhalation. The test was continued until either a fall of 20 percent or more in FEV1 was obtained or the last dose was reached. The results were expressed in terms of PD20, ie, the dose of methacholine producing a 20 percent fall in FEV1. Under these carefully controlled conditions, the 95 percent confidence intervals (as based on a single determination) corresponded to +/- 0.22 on a log10 scale or, in a more meaningful way, +/- 1.66 fold-difference in PD20 from one visit to the other.

Serial M-mode echocardiography in evaluation of the cardiovascular effects of tiapamil and their relationship to plasma levels in patients with coronary heart disease.

Tiapamil (Ro 11-1781) is a new calcium antagonist. Several investigators have reported about its efficacy against cardiac arrhythmias and angina pectoris. However, there was no study that assessed a possible relationship between hemodynamic effects and plasma concentration. Our study was aimed to investigate any possible relationship between cardiovascular effects of tiapamil and its plasma concentration. We selected 8 coronary; patients (6 males and 2 females) with a mean age of 61.9 yr and a mean weight of 70.9 kg. Tiapamil was administered per os at the dose of 250 mg t.i.d. for 4 consecutive days. Hemodynamic data were obtained by means of echocardiography, ECG and sphygmomanometry. Plasma concentrations of Ro 11-1781 and its major metabolites were measured by means of high pressure liquid chromatography. With tiapamil, the morning systolic BP fell from 130.6 +/- 19.5 (mean +/- SD, pretreatment) to 114.4 +/- 18.2 mm Hg on day 4, the change being clinically and statistically significant (P less than 0.02 by paired t-tests). Diastolic BP and HR remained unchanged. LVEDD and LVESD were not affected to any relevant extent, but VCF was significantly (P less than 0.05) and persistently increased. Tiapamil was well absorbed, but large interindividual variations were observed. As a general rule, no direct relationship between plasma concentrations and hemodynamic effects could be demonstrated. However, the number of patients is too small to allow general conclusions. At the above dose, tiapamil did not elicit any clinically detectable negative inotropic or negative chronotropic effect, probably because of its lowering effect on systolic BP.

Carbohydrate-induced thermogenesis in liver cirrhosis: glucose vs. fructose.

Reduced thermic response after a glucose load has been reported in liver cirrhosis. To determine the mechanism and the site of this phenomenon, the effects of glucose and fructose on energy expenditure (EE) were measured in seven well-nourished cirrhotic patients and in six healthy control subjects. EE and fuel utilization were measured via indirect calorimetry for 3 h after oral glucose or fructose administration (1 g/kg body wt). After a glucose load, plasma glucose and insulin concentrations were higher in cirrhotic patients than in control subjects (p < 0.05). During the glucose trial, the cumulative incremental changes in EE over the 3-h measurement period were lower (p < 0.01) in patients than in the control subjects (0.98 +/- 0.13 vs. 1.70 +/- 0.23 kJ.kg-1.3 h-1). After fructose ingestion, the cumulative changes in the EE of control subjects (1.76 +/- 0.24 kJ.kg-1.3 h-1) and cirrhotic patients (1.59 +/- 0.15 kJ.kg-1.3 h-1) were similar. In cirrhotic patients, the EE increase after fructose was higher than after glucose (p < 0.05). After glucose and fructose ingestion, no difference was observed between the carbohydrate oxidation in cirrhotic patients and that in control subjects, and lipid oxidation was suppressed to the same extent in both groups. We conclude that glucose-induced thermogenesis is impaired in liver cirrhosis, whereas fructose can normalize the thermic response. Because fructose is chiefly metabolized in the liver, these findings suggest that extrahepatic tissues are the site of defective thermogenesis in liver cirrhosis.

Different hemodynamic (24-h ambulatory blood pressure monitoring) and renin-inhibiting effect of a 1-week treatment with enalapril and lisinopril.

Ambulatory blood pressure and heart rate monitoring were used for comparing the antihypertensive effect of a 1-week treatment with enalapril and lisinopril 10 mg once daily (double-blind crossover placebo-controlled study). Twelve outpatients with mild to moderate hypertension were treated. Both drugs had a significant and identical hypotensive effect. Neither drug affected the diurnal rhythm of blood pressure or heart rate. Therefore the two drugs are equipotent antihypertensive agents. Both drugs inhibited ACE activity to a highly significant extent, but in this regard lisinopril was more effective than enalapril. However, lisinopril's greater ACE inhibition was not accompanied by a greater hypotensive effect. The clinical value of this difference is not yet established.

Dimeditiapramine (Ro 11-1781), a new calcium antagonist, in the management of supraventricular tachyarrhythmias in patients with acute myocardial infarction.

18 patients with acute myocardial infarction and sustained arrhythmias were treated with a new Ca2+ antagonist, Ro 11-1781, at the dose of 1.0 mg/kg i.v. The drug was effective in reducing heart rate to less than 90 beats/min in 9/10 patients with atrial fibrillation, in 3/4 patients with atrial flutter and in 3/4 patients with supraventricular tachycardia. The peak effect was observed within 2--5 min after the intravenous administration of Ro 11-1781. In cases with recurring tachyarrhythmias, the drug was also effective in repetitive administration. Systolic blood pressure was reduced, but severe hypotension (less than 90 mm Hg) was not observed. The atrioventricular conduction in these patients remained unimpaired and asystole did not occur. The drug appears to be an effective and a well tolerated antiarrhythmic agent.

Human electropharmacology of the calcium antagonist dimeditiapramine (Ro 11-1781) in coronary patients.

The electrophysiological effect of dimeditiapramine (Ro 11-1781), a Ca2+ antagonist, was evaluated in 20 patients with coronary heart disease. Electrophysiological measurements, including sinus cycle length, sinoatrial conduction time, intra-atrial conduction time, atrial, atrioventricular, nodal and ventricular refractory periods and intraventricular conduction time were recorded before and after the intravenous administration of Ro 11-1781. At a dose which is effective against cardiac arrhythmias, Ro 11-1781 produced no statistical significant changes in the sinoatrial and intraventricular conduction time. Similarly, neither the sinoatrial nor the ventricular refractory period was affected. Ro 11-1781, however, increased the atrioventricular conduction time and decreased the systolic blood pressure to a statistically significant extent. The tolerance was very good.

Cardiac risk of speed traps.

Twenty-two patients with stable cardiac disease drove into a radar trap while having an ambulatory electrocardiogram. All patients reported cardiac symptoms, heart rate increases, and appearance of repetitive ventricular arrhythmias. Myocardial ischemia was observed in some patients. Being caught while car speeding under the stresses of daily life may induce potentially dangerous cardiac effects. The data confirm the effects of stress and adrenergic tone on ventricular arrhythmias.

An evaluation of the safety of the beta-modulator cicloprolol in chronic heart failure.

The new beta-adrenoceptor partial agonist cicloprolol acts as a beta-agonist at normal levels and as a beta-antagonist at high levels of adrenergic discharge. Treatment with cicloprolol should protect the heart against excessive stimulation, while providing a baseline level of sympathetic drive. The clinical interest of such a profile is, however, not yet established in heart failure. Accordingly this study examined the safety of oral cicloprolol, a step necessary before undertaking efficacy comparison with other compounds recently proposed to treat heart failure. Twenty-five patients were studied. Cicloprolol was given once a day for 2 weeks in a crossover double-blind placebo-controlled design. Follow-ups were obtained at baseline and at the end of each period. At baseline all patients had clear evidence of heart failure. Cicloprolol did not affect resting heart rate and blood pressure, but it reduced significantly peak exercise heart rate and peak rate-pressure product. The effect was especially significant in patients with sinus rhythm. The drug did not induce bradycardia or arrhythmias. Resting and exercise ejection rate were not affected. Cicloprolol improved the quality of life and the work capacity of 5 of 12 patients with congestive failure due to ischemic etiology. Side effects were few and similar with placebo and cicloprolol. Thus, short-term administration of cicloprolol is safe in moderate heart failure.

Ergometric evaluation of the effects of enalapril maleate in normotensive patients with stable angina.

The anti-ischemic effect of a single oral dose of 10 mg of enalapril maleate (E) was investigated in 14 normotensive patients with coronary artery disease (CAD) and stable effort-induced angina pectoris. An exercise stress test was performed three times in each patient at the same clock hour on three successive days: with no treatment (baseline), 6 h after administration of placebo (P), and 6 h after oral administration of a single 10 mg dose of E. The multistage nonstop effort tests were performed in the sitting position. Workload started at 25 W and was increased by 25 W every 2 min until an ischemic ST depression of more than 1.5 mm was observed. The following parameters were measured: heart rate (HR), systolic blood pressure (BP), rate-pressure product (RPP), workload sustained (WS), elapsed time of effort (ET), and millimeters of ischemic ST depression. The values of the parameters observed with baseline, P, and E were compared at the moment of appearance of chest pain or ischemic ST depression, at the moment of maximal effort, maximal common WS (MCWS), and maximal common RPP (MCRPP). Enalapril delayed the appearance of the ischemic ST depression. At the MCWS, the RPP was significantly lower under E and the ST depression was less marked; this effect was the result of a lower BP level, in the absence of any significant change in HR response. The acute effects of E observed in normotensive patients with effort-induced angina pectoris seems to be related to the inhibition of angiotensin at the coronary level and to its antiadrenergic action.

The effect of amlodipine and enalapril on blood pressure and neurohumoral activation in hypertensive patients with Ribbing's disease (multiple epiphysal dystrophy).

BACKGROUND: In patients with Ribbing's disease (RD)--a form of multiple epiphysal dystrophy--hypertension is frequent, often severe, and accompanied by a relevant cardiac dysfunction. HYPOTHESIS: This study was undertaken to evaluate the contribution of the calcium antagonist amlodipine and of the angiotensin-converting-enzyme inhibitor enalapril to blood pressure regulation by studying their effect on neurohormonal activation. METHODS: Fifty hypertensive patients with RD were studied. After a placebo run-in period of 4 to 6 weeks, patients were randomly assigned to receive either amlodipine (10 mg once daily) or enalapril (20 mg once daily) for 6 months. RESULTS: Both drugs significantly lowered blood pressure. Enalapril did not result in activation of the sympathetic system (as determined by measurement of the plasma norepinephrine level). On the other hand, the hypotensive effect of amlodipine occurred with an increase in heart rate and in the levels of plasma norepinephrine and angiotensin II. CONCLUSION: It is unclear whether amlodipine may reduce cardiac dysfunction in patients with RD.