First operation in SPIDER and the path to complete MITICA.

The requirements of ITER neutral beam injectors (1 MeV, 40 A negative deuterium ion current for 1 h) have never been simultaneously attained; therefore, a dedicated Neutral Beam Test Facility (NBTF) was set up at Consorzio RFX (Padova, Italy). The NBTF includes two experiments: SPIDER (Source for the Production of Ions of Deuterium Extracted from Rf plasma), the full-scale prototype of the source of ITER injectors, with a 100 keV accelerator, to investigate and optimize the properties of the ion source; and MITICA, the full-scale prototype of the entire injector, devoted to the issues related to the accelerator, including voltage holding at low gas pressure. The present paper gives an account of the status of the procurements, of the timeline, and of the voltage holding tests and experiments for MITICA. As for SPIDER, the first year of operation is described, regarding the solution of some issues connected with the radiofrequency power, the source operation, and the characterization of the first negative ion beam.

First experiments with the negative ion source NIO1.

Neutral Beam Injectors (NBIs), which need to be strongly optimized in the perspective of DEMO reactor, request a thorough understanding of the negative ion source used and of the multi-beamlet optics. A relatively compact radio frequency (rf) ion source, named NIO1 (Negative Ion Optimization 1), with 9 beam apertures for a total H(-) current of 130 mA, 60 kV acceleration voltage, was installed at Consorzio RFX, including a high voltage deck and an X-ray shield, to provide a test bench for source optimizations for activities in support to the ITER NBI test facility. NIO1 status and plasma experiments both with air and with hydrogen as filling gas are described. Transition from a weak plasma to an inductively coupled plasma is clearly evident for the former gas and may be triggered by rising the rf power (over 0.5 kW) at low pressure (equal or below 2 Pa). Transition in hydrogen plasma requires more rf power (over 1.5 kW).

Installation of a versatile multiaperture negative ion source.

Neutral Beam Injectors (NBI), which need to be strongly optimized in the perspective of DEMO reactor, request a thorough understanding of the negative ion source used and of the multi-beamlet optics. A relatively compact RF ion source, named NIO1 (Negative Ion Optimization 1), with 9 beam apertures for a total H(-) current of 130 mA, 60 kV acceleration voltage, is being installed at Padua, in Consorzio RFX, to provide a test bench for source optimizations in the framework of the accompanying activities in support to the ITER NBI test facility. NIO1 construction and status of the overall installation, including a high voltage deck and an optical cavity ring down spectrometer are here summarized and reported. Plasma and low voltage beam operations are discussed. Development of a sampling beam calorimeter (with small sampling holes, and a segmented cooling circuit) is also discussed.

Development of a versatile multiaperture negative ion source.

A 60 kV ion source (9 beamlets of 15 mA each of H(-)) and plasma generators are being developed at Consorzio RFX and INFN-LNL, for their versatility in experimental campaigns and for training. Unlike most experimental sources, the design aimed at continuous operation. Magnetic configuration can achieve a minimum ∣B∣ trap, smoothly merged with the extraction filter. Modular design allows for quick substitution and upgrading of parts such as the extraction and postacceleration grids or the electrodes in contact with plasma. Experiments with a radio frequency plasma generator and Faraday cage inside the plasma are also described.

Design of a versatile multiaperture negative ion source.

Negative ion sources are a key component of the neutral beam injector to be installed in the International Thermonuclear Experimental Reactor. At present research and development activities address several important issues related to beam extraction, optics, and optimization. Together with the design of real size devices and the accumulation of atomic cross section databases, a relatively small negative ion source [130 mA of H(-) at 60 kV, named Negative Ion Optimization phase 1 (NIO1)] is under construction at Consorzio RFX to contribute to benchmark numerical simulation tools and to test components, such as emittance scanners, beam dumps, and cesium ovens. NIO1 design, magnet configuration, and rf coupling simulations are described.

Coronary stenting beyond standard indications. Immediate and follow-up results.

BACKGROUND: Coronary stent has become an accepted treatment modality for selected indications. However, the literature shows diverse results when indications for coronary stenting are different from those tested in large randomized trials. The purpose of this study was to determine immediate and follow-up clinical and angiographic results in patients treated with coronary stenting for indications not specifically tested in large randomized trials. METHODS: Coronary stents were implanted in a total of 2060 lesions (1757 patients) in seven groups with expanded indications: left main coronary lesions, calcified lesions, small vessels (< 3 mm in size), small vessels with diffuse disease, large vessels with diffuse disease, and bifurcation lesions treated with stents in both branches or with one stent implanted only in the major branch. Stents were implanted using high balloon pressure for final inflation and in most cases with intravascular ultrasound. Clinical follow-up was achieved in 96% of patients at a mean time of 12+/-7 months. RESULTS: Primary success (range 89-96%) and acute complications (range 5.7-13%) were comparable in all groups. At follow-up, the mortality rate was highest in the group of left main stenting (12.5%) but 20% of these patients had coronary stenting on non-elective basis. The restenosis rates ranged between 16-43%. The restenosis rate was highest in the group of bifurcation lesions with stent implantation in both vessels leading to a major adverse cardiac event (MACE) rate of 62% in this group. However, the survival rate at 1 and 2 years in the overall study group was 97 and 96%, and the event free survival was 76 and 74%, respectively. The procedure-related predictors of MACE were: final intravascular ultrasound result, use of stents with non-slotted tube morphology, final stent percent stenosis, and vessel size. CONCLUSIONS: Coronary stenting beyond standard indications is feasible, with acceptable primary success and complication rates. However, the overall MACE rates were relatively high (34-62%), in particular for the indication of bifurcation lesions with stents implanted in both vessels.

A prospective naturalistic study of 326 panic-agoraphobic patients treated with antidepressants.

OBJECTIVE: How far the results of randomized controlled studies apply to everyday care cannot be judged without regular measurements of outcomes in daily practice. We report on systematic data from a 3-year naturalistic prospective study on panic disorder-agoraphobic (PDA) patients treated with antidepressants in a setting of routine clinical practice. Our aim is to describe the evolution of PDA in relation to the treatments employed, and to explore demographic and clinical characteristics that might be predictive of outcome. METHODS: 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospective study. We utilized structured and semi-structures instruments, including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination. The main antidepressants used were imipramine (39%), clomipramine (28.5%) and paroxetine (23.3%); only 9% of patients received other antidepressants. RESULTS: 147 patients (45.1%) stayed on medication throughout the entire period of the follow-up. Of those who interrupted the treatment, 38% stayed in remission. The probability of achieving at least one remission during the 3-year follow-up period was 96.5% for PD and 95.9% for Agoraphobia. Relapses after a period of at least 2 months of complete remission were also common, and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1% for PD and 39% for Agoraphobia. The longest period of remission of PD is associated with low severity, medium-lasting course in patients with an onset of the illness in young adulthood. Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior. All three major drugs were reasonably well tolerated (only 9% dropped out because of side effects), with sexual dysfunction and increased appetite being the most common side effects at the last evaluation; in the first phase of the treatment anticholinergic effects and jitteriness were more common with TCAs. CONCLUSION: Both classical antidepressants and paroxetine emerge as a useful treatment in the long-term management of PDA; paroxetine appears particularly useful in PDA patients because it was significantly less likely to induce jitteriness, thereby reducing barriers to compliance.

Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens.

We investigated whether D1 dopaminergic receptors modulate in vivo acetylcholine output in the shell and core areas of rat nucleus accumbens using the microdialysis technique. Subcutaneous injection (1, 2 and 3 mg/kg) of the D1 agonist SKF 82958 enhanced acetylcholine output in both areas of the nucleus accumbens while the selective D1 antagonist SCH 39166 (0.15 and 0.30 mg/kg, s.c.) lowered it. Both SKF 82958 and SCH 39166 were more effective in the shell than in the core region. The increase in acetylcholine release induced by SKF 82958 in the shell was tetrodotoxin-sensitive. The dopamine release inducer d-amphetamine (1 and 2mg/kg, s.c.) and the dopamine uptake inhibitor cocaine (10 and 20 mg/kg, i.p.) dose-dependently raised acetylcholine release in the shell and core areas. The dopaminergic stimulants, like the direct-acting D1 compounds, were more effective in the shell than in the core compartment of the nucleus accumbens. The acetylcholine increases in the shell induced by d-amphetamine (2 mg/kg), cocaine (20 mg/kg) and SKF 82958 (3 mg/kg) were antagonized by the D1 antagonists SCH 39166 (5 microM) and SCH 23390 (10 microM), applied locally by reverse dialysis. The results suggest that dopamine acting at the D1 receptors exerts a tonic stimulatory control over the cholinergic function of the shell and core compartments of the nucleus accumbens with the shell being more strongly influenced.

Radial artery compliance in patients with peripheral vascular disease.

Compliance in largely central arteries of patients with peripheral vascular disease (PVD) has been reported to be reduced. However, the arterial tree is an inhomogeneous system, and there remains uncertainty about whether the peripheral arteries (e.g. the medium-sized muscular radial artery) undergo a similar change to the central arteries. The aim of this study was to investigate the radial artery elasticity in 19 patients with PVD compared with 18 normal subjects of comparable age and sex. Using a noninvasive high-resolution echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured the radial artery compliance by determining the diameter-pressure, compliance-pressure and distensibility-pressure curves. The results showed that the diameter of the radial artery was similar in the two groups, but that the compliance and distensibility were not further reduced in patients with PVD than in the normal controls at 100 mmHg and for a common blood pressure range. The present studies demonstrate that in patients with PVD the radial arterial compliance is not reduced, which indicates that the change in arterial elasticity is not identical. The potential mechanisms involved in this change in radial artery compliance are discussed.

[National Register of congenital hypothyroidism]. / Il registro nazionale degli ipotiroidei congeniti.

The results of five years activity of the National Register of children with Congenital Hypothyroidism (NRCH) have been evaluated. NRCH was established in Italy in 1987, as a pilot project of Health Ministry. All Italian Centers in charge of the screening, treatment and follow-up of CH are involved in the program. The results have provided further epidemiological informations about CH in Italy and have evidenced some aspects in the screening organization which had to be improved. Discussion of Register data in annual meetings has recently allowed to obtain an improvement especially for the beginning of treatment and the used dose of therapy.

MODDIS: a microcomputer program for model discrimination.

A computer program for a microcomputer (HP 86) is presented to discriminate between different models and to design new experiments for model discrimination. By a non-linear fitting algorithm a set of experimental data is fitted with different models suggested by the user. The parameters characterizing each model are estimated by minimizing the sum of squared residuals; different criteria are used to test the choice between two or more models at different levels of probability and the smallest number of additional experiments required for discrimination is computed. If discrimination is not achieved a direct search method is used to find the local maxima of the divergence (or information for discrimination) over a user-chosen domain of independent variables (x R'''). The x value corresponding to the absolute maximum of the divergence is the best choice to run a new experiment for discrimination.

Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test.

The effect of loperamide and naloxone on mouth-to-caecum transit time was evaluated by the lactulose hydrogen breath test in four men and four women. Each subject underwent tests during the administration of placebo, loperamide (12-16 mg po), naloxone (40 micrograms/kg/h by a three-hour intravenous infusion), and loperamide plus naloxone, carried out at intervals of one or two weeks. The transit time was significantly longer after loperamide, and this effect was antagonised by the concomitant administration of naloxone whereas naloxone administered alone had no effect on mean transit time. No clinically important side effects were reported.

Morphine tissue levels and reduction of gastrointestinal transit in rats. Correlation supports primary action site in the gut.

Overnight-fasted male rats given a single dose of tritium-labeled morphine either intraperitoneally or intravenously were fed a charcoal test meal by stomach tube. The drug remaining in tissues was assayed by liquid scintillation counting of thin-layer chromatograms from homogenates, and gastrointestinal transit was tested by measuring the portion of the small intestine traversed by charcoal in 5 min. Morphine, 0.15 mg/kg, given intraperitoneally either 10 min or 30 min before testing substantially reduced gastrointestinal transit (to 23% and 55% of drug-free controls, respectively), and produced maximum drug levels 5 min after administration in small intestine longitudinal muscle with attached myenteric plexus (500 +/- 42 ng/g, mean +/- SE, n = 4). Intact small intestine, plasma, and brain, respectively, contained decreasing drug concentrations that, in the latter, never exceeded 2%-3% of that in longitudinal muscle. Rats receiving 0.15 mg/kg morphine intravenously presented only minor and short-lived inhibition of gastrointestinal transit that was significantly below (approximately 35%) that of drug-free controls at 10 min, but not 30 min, after drug administration. Morphine levels in the brain and plasma of these rats were up to five times higher, and in the intact small intestine longitudinal muscle were up to 20 times lower than in intraperitoneally treated rats. Morphine concentration in the tissues assayed was plotted against the effect on gastrointestinal transit at the same interval for individual rats regardless of dose, administration route, and observation time: data analysis, in small intestine longitudinal muscle, but not in the brain or plasma, indicated a highly significant correlation and fitting of computer-generated curves described by a currently accepted equation according to the receptor occupation theory of drug response. In view of these findings, and of the complete prevention by the "peripherally selective" narcotic antagonist N-methyl naloxone of gastrointestinal transit inhibition after an intravenous analgesic dose of morphine (1 mg/kg), the investigated animal model is consistent with the primary role of a gut-located action site in opiate-induced constipation.

Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase.

Mouse strains with different susceptibility to aryl hydrocarbon hydroxylase (AHH) induction and with different levels and/or affinity for a specific cytosolic binding protein ("receptor") were used to investigate the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Humoral antibody production was strongly inhibited in C57Bl/6 and C3H/HeN mice (more susceptible strains) with very low, single doses of TCDD (1.2 micrograms/kg), while other strains (DBA/2 and AKR) required higher doses (at least 6 micrograms/kg) to be partially suppressed. Longer exposure (8 weeks) did not increase the sensitivity of DBA/2 mice. A good correlation between the degree of enzyme inducibility and immunosuppression was observed in studies with B6D2F1 mice and backcrosses. Similar results were obtained with 2,3,7,8-tetrachlorodibenzofuran (TCDF), the most powerful competitor for TCDD "receptor" in vitro and in vivo. TCDD immunotoxic effects appeared to be associated with the presence of a specific cytosolic binding protein which mediates AHH induction.

The simulated randomization test.

Non-parametric statistical methods have been the subject of renewed interest. They are particularly useful in the behavioral sciences as they can be applied to a large class of distributions, and because the investigator is not forced into making any erroneous assumptions about a Gaussian distribution for the parent population or about equal variances in the contrasted groups. The randomization test is the most powerful non-parametric test [1] but it is rarely used because it calls for a prohibitive amount of computation. However, two tools now available make it more feasible: simulation and high-speed computer calculations. This test's importance lies in the extremely simple logic by which it is set up. The program described here is written in BASIC language for a microcomputer and carries out an approximate randomization test using a simulated distribution instead of the entire distribution. This version is slightly less powerful, a small price to pay for reducing the enormous calculation capacity otherwise required.

SPBS: statistical programs for biological sciences. Minicomputer software for applying routine biostatistical methods.

The main routine statistical analyses can be carried out from start to finish on a minicomputer with basic language capability and greater than or equal to 32000 bytes of random access memory. However, no statistical software packs for minicomputers are ever complete enough for exhaustive analysis of most problems. Taking account of the requirements of statistical models, this paper gives an outline of how to set up a program. Examples are given from the package of statistical programs developed at this institute. The advantages and disadvantages of making these analyses on minicomputers are discussed, in comparison with the use of statistical programs requiring large computers.

Walker carcinoma 256: a model for studies on tumor-induced anorexia and cachexia.

Data on anorexia and cachexia induced by Walker carcinoma 256 in Sprague-Dawley rats were analyzed in order to standardize an experimental model using a statistical (nondeterministical) procedure for assessing the efficacy of potential orexigenic agents. This model was characterized by a mean survival time of 14 +/- 1 days and by food intake and body weight loss starting from day 6 after tumor implantation. The complex course of cachexia was characterized by reduction in the weight of gastrocnemius muscle and epididymal adipose tissue, taken as representative sites of loss of proteins and lipids.

[Tiapride in the treatment of chronic headache (author's transl)]. / La tiapride nella terapia delle cefalee croniche.

The therapeutic efficacy of tiapride in chronic headache (300 mg/day orally during 30 days) was studied in a doubleblind trial in a group of 50 patients, 40 of them with so-called "mixed headache", and 10 with classical migraine. The results were subjected to statistical analysis. 65% of treated patients had clinical benefit in the intensity and frequency of headaches. The mode of action of this drug is discussed, together with the involvement of several monoaminergic systems in the genesis of headache. The action of tiapride appears to be indirectly dopaminomimetic as it operates by a blockade of dopaminergic inhibitors receptors.