International exercise on 124Sb activity measurements.

An international exercise, registered as EUROMET project no. 907, was launched to measure both the activity of a solution of (124)Sb and the photon emission intensities of its decay. The same solution was sent by LNE-LNHB to eight participating laboratories. In order to identify possible biases, the participants were asked to use all possible activity measurement methods available in their laboratory and then to determine their reference value for comparison. Thus, measurement results from 4pibeta-gamma coincidence/anti-coincidence counting, CIEMAT/NIST liquid-scintillation counting, 4pigamma counting with well-type ionization chambers and well-type crystal detectors were given. The results are compared and show a maximum discrepancy of about 1.6%: possible explanations are proposed.

International exercise on 124Sb photon emission intensities determination.

An international exercise, registered as EUROMET project no. 907, was launched to measure both the activity of a solution of (124)Sb and the photon emission intensities of its decay. The same solution was sent by LNE-LNHB to eight participating laboratories, six of which sent results for photon emission intensities both in absolute and in relative terms. From these results and including previous published values, a consistent decay scheme was worked out, proving that problems in activity measurements have not been due to decay scheme data.

On the variation of the 210Po half-life at low temperature.

Experiments were performed to verify the possible influence of the temperature and source matrix on the half-life of (210)Po. Since the precise measurement of the activity of an alpha-emitting source at cryogenic temperature is far from trivial, a simpler approach was used: the activity of a (210)Po source was measured at ambient temperature, but in between the measurements, the source was cooled down during a few weeks in a liquid helium Dewar. A (210)Po solid source was prepared by electro-deposition on a silver plate. The activity of this source was first measured at room temperature, using the defined solid angle alpha measurement method. The source was then placed in a specific gastight container inside a liquid helium bath at 4 K during 28 days. Then the source was heated up and measured again using the same instrument in the same geometric conditions. The same experiment was repeated with the source coated with a thin layer of silver, in order to be sure that the radioactive material was fully embedded inside the metallic matrix. Our experiments showed no evidence of (210)Po half-life change at low temperature. A reduction of the half-life of (210)Po by 6.3% at low temperature, as claimed by Raiola et al. (2007), would have lead to a decay-corrected activity reduction of about 1% after 29 days, which would have been easily detectable. The paper describes the steps of this experiment and gives a detailed uncertainty budget for the measurements. The half-life of (210)Po obtained in each measurement is compared with the evaluated value of (138.3763+/-0.0017) d.

First measurement of the beta spectrum of 241Pu with a cryogenic detector.

The LNE-LNHB is developing metallic magnetic calorimeters, a specific type of cryogenic detectors, for beta spectrometry. The aim is the determination of the shape factors of beta spectra. Our latest detector has been designed to measure the spectrum of (241)Pu, a pure beta emitter with an endpoint energy of 20.8 keV. In this paper, the detection principle of metallic magnetic calorimeters is explained and a detailed description is given of the realization of the detector enclosing a (241)Pu source inside the detector absorber. A spectrum resulting from our first measurement is shown and compared with a theoretical spectrum.

Comparative study of two drying techniques used in radioactive source preparation: freeze-drying and evaporation using hot dry nitrogen jets.

Quantitative solid sources are used widely in the field of radionuclide metrology. With the aim to improve the detection efficiency for electrons and x-rays, a comparative study between two source drying techniques has been undertaken at LNE-Laboratoire National Henri Becquerel (LNE-LNHB, France). In this paper, freeze-drying using commercial equipment is compared with a system of drying using hot jets of nitrogen developed at Institute for Reference Materials and Measurements (IRMM, Belgium). In order to characterize the influence of self-absorption, the detection efficiencies for (51)Cr sources have been measured by coincidence counting and photon spectrometry.

Validation study of a new technique for absolute activity measurement with 4pi solid angle metallic magnetic calorimeters.

In this paper we present a prototype of a new class of detectors, metallic magnetic calorimeters operating at cryogenic temperatures, which we are developing for absolute activity measurement of low-energy-emitting radionuclides. We explain the detection principle and give a detailed description of the realisation of the prototype, containing an (55)Fe source inside the detector absorber. The analysis of first data taken with this detector is presented and the result of activity measurement compared with liquid scintillation counting. Some ways for reducing the uncertainty that can be achieved with this new technique are proposed.

High-energy resolution X-ray, gamma and electron spectroscopy with cryogenic detectors.

Cryogenic detectors offer remarkably better energy resolutions than those achievable with conventional semiconductor or scintillation detectors. With the additional asset of a detection efficiency close to unity for low-energy X-ray photons and electrons, these detectors have the potential to perform X-ray, gamma and electron spectroscopy of a hitherto unknown quality, in particular at low energies. Two types of cryogenic detectors are described and the results of prototype detectors are presented.

Safety, tolerance, and pharmacokinetics of atevirdine mesylate (U-87201E) in asymptomatic human immunodeficiency virus-infected patients.

Atevirdine mesylate (U-87201E) is a new nonnucleoside (bisheteroarylpiperazine) inhibitor of human immunodeficiency virus type 1 reverse transcriptase. In a double-blind, escalating single-dose study the safety, tolerance, and pharmacokinetics of atevirdine mesylate were investigated in 24 asymptomatic human immunodeficiency virus-seropositive male patients. Each patient received one single oral dose of atevirdine mesylate and placebo separated by an interval of 1 to 3 weeks. For each dose level (400, 800, 1,200, and 1,600 mg) six patients received drug and placebo on separate occasions. Blood samples were collected before dosing and at intervals afterward for safety evaluation and estimation of atevirdine and metabolite levels. The concentrations of atevirdine and its principal metabolite (U-89255) in serum were determined by high-performance liquid chromatography. The results of the study showed that atevirdine mesylate is well tolerated at all dose levels. No clinically significant effects on vital signs, electrocardiograms, or laboratory tests were observed. Occasional headache and nausea were reported both in the drug group and in the placebo group. The times to peak values were relatively short (0.5 to 1.0 h), suggesting a rapid absorption. The maximum concentrations of drug in serum were 1.4 microM (400 mg), 4.2 microM (800 mg), 7.3 microM (1,200 mg), and 5.8 microM (1,600 mg). The values of the pharmacokinetic parameters for atevirdine were found to have relatively large intersubject variabilities, and consequently, the study had little power to detect dose-dependent changes in the values of the pharmacokinetic parameters. The oral clearance of atevirdine tended to increase by 90% as the atevirdine mesylate doses increased from 400 to 1,600 mg, but this change in oral clearance was not statistically significant. The values of the pharmacokinetic parameters determined in the study were similar to those found in a previous single-dose study in healthy volunteers.

Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis.

The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis.

Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients.

A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram-positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram-positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram-positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram-negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes.