High flux circularly polarized gamma beam factory: coupling a Fabry-Perot optical cavity with an electron storage ring.

We report and discuss high-flux generation of circularly polarized γ-rays by means of Compton scattering. The γ-ray beam results from the collision of an external-cavity-enhanced infrared laser beam and a low emittance relativistic electron beam. By operating a non-planar bow-tie high-finesse optical Fabry-Perot cavity coupled to a storage ring, we have recorded a flux of up to (3.5 ± 0.3) × 108 photons per second with a mean measured energy of 24 MeV. The γ-ray flux has been sustained for several hours. In particular, we were able to measure a record value of up to 400 γ-rays per collision in a full bandwidth. Moreover, the impact of Compton scattering on the electron beam dynamics could be observed resulting in a reduction of the electron beam lifetime correlated to the laser power stored in the Fabry-Perot cavity. We demonstrate that the electron beam lifetime provides an independent and consistent determination of the γ-ray flux. Furthermore, a reduction of the γ-ray flux due to intrabeam scattering has clearly been identified. These results, obtained on an accelerator test facility, warrant potential scaling and revealed both expected and yet unobserved effects. They set the baseline for further scaling of the future Compton sources under development around the world.

External cavity enhancement of picosecond pulses with 28,000 cavity finesse.

We report on the first demonstration, to the best of our knowledge, of the locking of a Fabry-Perot cavity with a finesse of 28,000 in the pulsed regime. The system is based on a stable picosecond oscillator, an ultrastable cavity with high-reflection mirrors, and an all-numerical feedback system that allows efficient and independent control of the repetition rate and the pulse to pulse carrier-to-envelop phase drift (CEP). We show that the carrier to envelop phase can have a dramatic effect even for pulses with hundreds of cycles. Moreover, we have succeeded in unambiguously measuring the CEP of a 2 ps pulse train. Finally, we discuss the potential of our findings to reach the MW average power level stored in an external cavity enhancement architecture.

Temporally controlled modulation of antihydrogen production and the temperature scaling of antiproton-positron recombination.

We demonstrate temporally controlled modulation of cold antihydrogen production by periodic RF heating of a positron plasma during antiproton-positron mixing in a Penning trap. Our observations have established a pulsed source of atomic antimatter, with a rise time of about 1 s, and a pulse length ranging from 3 to 100 s. Time-sensitive antihydrogen detection and positron plasma diagnostics, both capabilities of the ATHENA apparatus, allowed detailed studies of the pulsing behavior, which in turn gave information on the dependence of the antihydrogen production process on the positron temperature T. Our data are consistent with power law scaling T (-1.1+/-0.5) for the production rate in the high temperature regime from approximately 100 meV up to 1.5 eV. This is not in accord with the behavior accepted for conventional three-body recombination.

Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis.

INTRODUCTION: Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease. AIM: To investigate factors potentially preventing atherosclerosis in PBC patients. METHODS: Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 +/- 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome. RESULTS: The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 +/- 50.5 mg/dL in PBC vs 221.7 +/- 39.7 mg/dL in NASH vs 209.8 +/- 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase. CONCLUSIONS: The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is a multifactorial disorder of pregnancy associated with a genetic background. AIM: To evaluate the genetic contribution of ABCB4, MDR3 gene in the development of intrahepatic cholestasis of pregnancy in a large cohort of Italian subjects. METHODS: This study represents an extension of a previous multicentre-prospective study including three Italian referral centres. In all, we enrolled 96 women at the 3rd trimester of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes by standard procedures. Polymerase chain reaction was used to amplify exon 14, 15 and 16 of MDR3 gene. RESULTS: We found 3 non-synonymous heterozygous mutations in exon 14 (E528D, R549H, G536A), 1 in exon 15 (R590Q) and 2 in exon 16 (R652G, T6671). MDR3 gene variants in exons 14, 15 and 16 occurred in 7/96 of pregnant mothers with intrahepatic cholestasis of pregnancy (7.2%), and in none of 96 pregnant controls matched for age and parity. All seven patients had normal gamma-glutamyl transpeptidase, normal bilirubin, but high levels of both alanine transferase and serum bile acids. One had cholesterol biliary lithiasis. The outcome of pregnancy was normal in four cases (with vaginal delivery), while there was one fetal distress. CONCLUSIONS: MDR3 mutations are responsible for the development of intrahepatic cholestasis of pregnancy in only a small percentage of Italian women. Further genetic studies are warranted, however, to clarify the role of different mutations in intrahepatic cholestasis of pregnancy.

Evidence for the production of slow antiprotonic hydrogen in vacuum.

We present evidence showing how antiprotonic hydrogen, the quasistable antiproton (p)-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion H2+ in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events, evidence is presented for antiprotonic hydrogen production with sub-eV kinetic energies in states around n=70, and with low angular momenta. The slow antiprotonic hydrogen may be studied using laser spectroscopic techniques.

Search for laser-induced formation of antihydrogen atoms.

Antihydrogen can be synthesized by mixing antiprotons and positrons in a Penning trap environment. Here an experiment to stimulate the formation of antihydrogen in the n = 11 quantum state by the introduction of light from a CO2 continuous wave laser is described. An overall upper limit of 0.8% with 90% C.L. on the laser-induced enhancement of the recombination has been found. This result strongly suggests that radiative recombination contributes negligibly to the antihydrogen formed in the experimental conditions used by the ATHENA Collaboration.

Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations.

BACKGROUND: The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified. AIM: To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects. METHODS: We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit. RESULTS: Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third. CONCLUSIONS: These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.

New source of dense, cryogenic positron plasmas.

We have developed a new method, based on the ballistic transfer of preaccumulated plasmas, to obtain large and dense positron plasmas in a cryogenic environment. The method involves transferring plasmas emanating from a region with a low magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure better than 10(-13) mbar. The achieved positron accumulation rate in the high field cryogenic trap is more than one and a half orders of magnitude higher than the previous most efficient UHV compatible scheme. Subsequent stacking resulted in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4 higher than previously reported. Using a rotating wall electric field, plasmas containing about 20 x 10(6) positrons were compressed to a density of 2.6 x 10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

Spatial distribution of cold antihydrogen formation.

Antihydrogen is formed when antiprotons are mixed with cold positrons in a nested Penning trap. We present experimental evidence, obtained using our antihydrogen annihilation detector, that the spatial distribution of the emerging antihydrogen atoms is independent of the positron temperature and axially enhanced. This indicates that antihydrogen is formed before the antiprotons are in thermal equilibrium with the positron plasma. This result has important implications for the trapping and spectroscopy of antihydrogen.

Three-dimensional annihilation imaging of trapped antiprotons.

We demonstrate three-dimensional imaging of antiprotons in a Penning trap, by reconstructing annihilation vertices from the trajectories of the charged annihilation products. The unique capability of antiparticle imaging has allowed, for the first time, the observation of the spatial distribution of the particle loss in a Penning trap. The radial loss of antiprotons on the trap wall is localized to small spots, strongly breaking the azimuthal symmetry expected for an ideal trap. Our observations have important implications for detection of antihydrogen annihilations.

Positron plasma diagnostics and temperature control for antihydrogen production.

Production of antihydrogen atoms by mixing antiprotons with a cold, confined, positron plasma depends critically on parameters such as the plasma density and temperature. We discuss nondestructive measurements, based on a novel, real-time analysis of excited, low-order plasma modes, that provide comprehensive characterization of the positron plasma in the ATHENA antihydrogen apparatus. The plasma length, radius, density, and total particle number are obtained. Measurement and control of plasma temperature variations, and the application to antihydrogen production experiments are discussed.

Production and detection of cold antihydrogen atoms.

A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem-experimental investigations involving comparisons of particles with antiparticles are numerous. Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN) and at Fermilab, but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.

Isolated noncompaction of the myocardium: an exceedingly rare cardiomyopathy. A case report.

Isolated noncompaction of the left ventricular myocardium is a rare cardiac disorder due to an arrest in myocardial morphogenesis. It is characterized by prominent and excessive trabeculation in a ventricular wall segment, with deep intertrabecular spaces perfused from the ventricular cavity. Echocardiographic findings are important clues for the diagnosis. Clinical symptoms include signs of left ventricular systolic dysfunction even to the point of heart failure, ventricular arrhythmias, and embolic events. We describe an adult case in whom the only clinical symptoms were life-threatening ventricular arrhythmias. Transthoracic echocardiography did not contribute to the diagnosis, which was made thanks to left ventricular contrast angiography. Electrophysiological testing induced a fast monomorphic sustained ventricular tachycardia, with hemodynamic impairment, that was refractory to pharmacological treatment, and for this reason a permanent cardioverter-defibrillator was implanted. A subsequently performed transesophageal echocardiographic examination showed a localized, regional increase in left ventricular wall thickness and degree of trabeculation. The causes and electrophysiological mechanisms of arrhythmias in noncompaction are still unknown: grossly irregular branching and connecting of myocardial fascicles in the noncompacted segments, isometric contraction with increased wall stress, and localized coronary perfusion impairment can all induce disorganized or delayed activation and increase the potential for arrhythmias. This is the first reported case of noncompaction in which an implantable defibrillator was used to control life-threatening arrhythmias.

[The exercise test with atropine]. / Il test da sforzo con atropina.

BACKGROUND: Exercise testing remains the most accessible and widely used technique for the detection of coronary artery disease (CAD) and for the assessment of its severity. Clinical usefulness of the simple exercise test is limited by poor sensitivity and imperfect specificity. Many patients referred for diagnostic stress testing cannot achieve an adequate increase in heart rate due to lack of motivation, poor physical condition, or medications. Atropine increases the heart rate and therefore myocardial oxygen consumption, and might improve the diagnostic accuracy of exercise testing, either reducing the number of non-diagnostic examinations, or increasing the positivity of the test in patients with non severe coronary disease. METHODS: One-hundred-seventy-two consecutive patients (144 males and 28 females, age 58 +/- 8 years) with suspected coronary artery disease underwent exercise testing and coronary angiography. Exercise testing was considered positive in the presence of ST segment depression > or = 0.10 mV horizontal or downsloping, > or = 0.15 mV upsloping, or in the presence of ST elevation without Q waves. The test was considered negative in the absence of significant ST depression or elevation if the exercise heart rate was > 85% of age-predicted maximum, non-diagnostic if the heart rate was < 85%. In 148 patients (86%) coronary angiography showed CAD (> 70% luminal reduction in at least one major vessel), in 24 patients (14%) non significant CAD or angiographically normal coronary arteries (NoCAD). Exercise testing was positive in 134 patients (78%: 85% in CAD, 33% in NoCAD), negative in 13 patients (8%: 3% in CAD, 38% in NoCAD), non-diagnostic in 25 patients (14%; 12% in CAD, 29% in NoCAD). The sensitivity was 85%, specificity was 38%, and diagnostic accuracy 78%. In the 25 patients with non-diagnostic test (18 CAD, 7 NoCAD) the exercise was repeated 30-90 minutes later, immediately after i.v. injection of 1-2 mg of atropine, and was stopped at the same workload of the index test. RESULTS: The atropine-exercise test was well tolerated and accomplished in all cases. The maximal heart rate (139 +/- 11 vs 121 +/- 11) and the double product (25,308 +/- 4082 vs 22,166 +/- 3569) were significantly greater after atropine. The increase of the maximal heart rate improved the detection of the electrocardiographic signs of exercise-induced myocardial ischemia only in CAD patients. In the 18 CAD patients the atropine-exercise test was positive in 8, negative in 5, non-diagnostic in 5. In the 7 NoCAD patients the atropine-exercise test was positive in 1, negative in 6. The test remained non-diagnostic only in 3% of patients. The sensitivity of the test with atropine was 91%, specificity was 63%, and diagnostic accuracy 87%. CONCLUSIONS: The addition of atropine to exercise testing, which causes further chronotropic stress to the myocardium, is well tolerated and safe, and improves the diagnostic accuracy of the test for the detection of coronary artery disease in patients who cannot achieve an adequate exercise heart rate. The combination with atropine increases the utility and the cost-effectiveness of exercise testing.

Digital stress-echocardiography using a public domain program for the Macintosh personal computer.

Left ventricular wall motion abnormalities secondary to stress-induced myocardial ischemia can be detected with difficulty by mentally comparing echocardiographic images sequentially recorded on videotape. Digital stress-echocardiography, a combination of ultrasound imaging and digital archiving technologies, at least partially can overcome this problem: the technique is based on reviewing images at rest and after stress (exercise or pharmacological) side by side in dual- or quad-screen digital format, in a synchronized cine-loop, as if obtained simultaneously. This technique however is presently not widely used, due to the high cost of most commercially available systems. We have developed a digital stress-echo system, which is easy to use and relatively inexpensive, running on a Macintosh II personal computer with 8-bit graphics. The 2-D echocardiographic images recorded on videotape are digitized offline using a video digitizing board. The image can be displayed and analyzed using the public domain NIH image software developed by Wayne Rasband, without loss in image quality and resolution, particularly if using Super-VHS videotape. We have made a macro procedure for the montage in a quad-screen format of four digital recorded echocardiographic cardiac cycles of six frames that takes only a little more time than commercially available systems. In conclusion, the use of a personal computer and low-cost software may help to make digital stress-echo techniques more widely feasible in the clinical setting and increase the diagnostic power of the ultrasound technique in the evaluation of patients with known or suspected coronary artery disease.

[Acute myocardial ischemia: ECG or echocardiography? Considerations on a clinical case]. / Ischemia miocardica acuta: ECG o ECO? Considerazioni su un caso clinico.

We present a clinical case and a review of the literature on the usefulness of two-dimensional echocardiography for the diagnosis of acute myocardial ischemia in patients presenting with chest pain but without diagnostic electrocardiographic changes. The case refers to a patient admitted a few hours after an episode of prolonged chest pain without diagnostic electrocardiographic changes, but with a severe wall motion abnormality assessed by two-dimensional echocardiogram. The electrocardiogram obtained 24 hours after admission showed giant negative T waves in the anterior chest leads when the patient was asymptomatic and the echocardiogram showed disappearance of wall motion abnormalities. Coronary angiography demonstrated a thrombotic occlusion of the left anterior descending coronary artery, that was treated by transluminal angioplasty. The considerations refer to the following points: 1) a substantial portion of patients with chest pain examined in the emergency room has initially a normal or non-diagnostic electrocardiogram; 2) in these patients two-dimensional echocardiography provides a highly sensitive and specific noninvasive tool for the establishment of the correct diagnosis of acute myocardial ischemia when a severe wall motion abnormality is shown; 3) if successive amelioration of regional myocardial dysfunction is assessed, this was probably due to stunned myocardium; 4) it is probably not correct to consider T wave inversion as the electrocardiographic equivalent of myocardial stunning, as the two phenomena are not chronologically correlated.

[Coronary angioplasty in postinfarct angina]. / L'angioplastica coronarica nell'angina postinfartuale.

BACKGROUND: The recurrence of transient myocardial ischemia is a frequent event in the course of acute myocardial infarction. Postinfarction angina develops more frequently after a non-Q wave infarction, and after effective thrombolysis; when uncontrolled by standard medical treatment, it is associated with an increased incidence of unfavorable cardiac events. Therapeutic strategies involve aggressive medical therapy, frequent use of early angiography, and mechanical coronary revascularization with bypass surgery or transluminal coronary angioplasty (PTCA). PATIENTS: We retrospectively examined 68 consecutive patients treated with PTCA for postinfarction angina. Of the whole, 36 (53%) had sustained a non-Q wave infarction; 29 (43%) had been treated with thrombolysis in the acute phase. Ischemia was in the infarction zone in 94% of cases; mean EF was 61.5 +/- 12%, and in 18 cases EF was < 55%. RESULTS: In 7 cases two arteries were dilated. There were no deaths related to the procedure. The overall success rate was 91.2%. Major complications occurred in 2 cases (1 acute occlusion with reinfarction, 1 major dissection requiring emergency surgery). The results are analyzed according to the time interval between index infarction and PTCA. In 28 cases (Group A) PTCA was performed within 30 days due to medically refractory symptomatology; in 40 cases (Group B) PTCA was postponed to beyond 30 days from infarction. In Group A involvement of the left anterior descending coronary artery was more frequent (75% of cases vs 40%; p = 0.009). The success rate in Group A was slightly lower than for Group B (85.7% vs 95%); the incidence of complications was higher (7.1% vs 0%), although not statistically different. At 6 month follow-up a restenosis was found in 10 cases (16% of successful PTCAs, 21% of angiographic controls). CONCLUSIONS: We conclude that for patients with postinfarction angina, selected for a suitable coronary anatomy, PTCA is an effective therapeutic option, with a high success rate, low immediate morbidity, and good mid-term results. The risk of intraprocedural complications appears only slightly higher for patients with unstable symptoms, who undergo PTCA earlier after infarction.

[Electrocardiographic monitoring of myocardial ischemia during coronary angioplasty correlated with results of the procedure]. / Evoluzione elettrocardiografica della ischemia miocardica durante angioplastica coronarica in correlazione con il risultato della procedura.

In 24 patients 2 leads Holter monitoring was performed during percutaneous transluminal coronary angioplasty (PTCA) of left anterior descending (17 patients), right coronary artery (6 patients), left circumflex (1 patient). In 20 patients (83%) significant ST segment deviations were recorded in the lead CM2 or RV. The following characteristics of ST segment deviation were analyzed during 7 +/- 3 successive occlusions: time to onset, maximal ST shift, slope to development, time to onset and slope of ST segment normalization. In 17 patients with successful PTCA the slope of ST segment normalization increased progressively from the first to the third-fifth inflation and then was constant. The improvement in ST segment normalization velocity was correlated (p less than 0.01) with the reduction of the diameter and with improvement of sectional area of the dilated vessel. The maximal ST segment normalization slope was correlated (p less than 0.01) with the diameter and the area of the residual stenosis. Continuous electrocardiographic recording, during PTCA, for evaluation of ST segment normalization velocity is a promising approach for monitoring the immediate result of coronary angioplasty.