Imaging low-mass planets within the habitable zone of α Centauri.

Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, α Centauri. Based on 75-80% of the best quality images from 100 h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of α Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around α Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes.

Development of a mirror-based endoscope for divertor spectroscopy on JET with the new ITER-like wall (invited).

A new endoscope with optimised divertor view has been developed in order to survey and monitor the emission of specific impurities such as tungsten and the remaining carbon as well as beryllium in the tungsten divertor of JET after the implementation of the ITER-like wall in 2011. The endoscope is a prototype for testing an ITER relevant design concept based on reflective optics only. It may be subject to high neutron fluxes as expected in ITER. The operating wavelength range, from 390 nm to 2500 nm, allows the measurements of the emission of all expected impurities (W I, Be II, C I, C II, C III) with high optical transmittance (≥ 30% in the designed wavelength range) as well as high spatial resolution that is ≤ 2 mm at the object plane and ≤ 3 mm for the full depth of field (± 0.7 m). The new optical design includes options for in situ calibration of the endoscope transmittance during the experimental campaign, which allows the continuous tracing of possible transmittance degradation with time due to impurity deposition and erosion by fast neutral particles. In parallel to the new optical design, a new type of possibly ITER relevant shutter system based on pneumatic techniques has been developed and integrated into the endoscope head. The endoscope is equipped with four digital CCD cameras, each combined with two filter wheels for narrow band interference and neutral density filters. Additionally, two protection cameras in the λ > 0.95 µm range have been integrated in the optical design for the real time wall protection during the plasma operation of JET.

The flight experiment ANITA--a high performance air analyser for manned space cabins.

Analysing Interferometer for Ambient Air (ANITA) is a flight experiment as precursor for a permanent continuous trace gas monitoring system on the International Space Station (ISS). For over 10 years, under various ESA contracts the flight experiment was defined, designed, breadboarded and set up. For the safety of the crew, ANITA can detect and quantify quasi on-line and simultaneously 32 trace gases with ppm or sub-ppm detection limits. The self-standing measurement system is based on Fourier Transform Infrared Spectrometer (FTIR) technology. The system represents a versatile air monitor allowing for the first time the detection and monitoring of trace gas dynamics of a spacecraft atmosphere. It is envisaged to accommodate ANITA in a Destiny (US LAB) Express Rack on the ISS. The transportation to the ISS is planned with the first ATV 'Jules Verne'. The options are either the Space Shuttle or the Automated Transfer Vehicle.

Four patients with AL amyloidosis treated with high-dose chemotherapy and autologous stem cell transplantation.

Four patients with AL amyloidosis underwent high-dose chemotherapy and autologous stem cell transplantation at our institutions. Here, we report the clinical courses and outcomes in these patients. Two patients with multi-organ amyloid deposits including cardiac involvement died within 12 days after high-dose chemotherapy. However, in the other two patients, one of whom was suffering from amyloid-related cardiac failure, a significant improvement of organ function was achieved.

Severe panarteritis associated with drug abuse.

A case of panarteritis with purpura fulminans, mononeuritis multiplex, gastrointestinal manifestation and presumably cardiac involvement in a previously healthy 22-year-old man with a history of drug abuse including cocaine, cannabinoids and methamphetamines is described. Histopathological examination of the gut led to the diagnosis of panarteritis without immune deposits. Antineutrophil antibodies were negative. Besides the drugs, no other possible cause of vasculitis was found. The patient recovered completely after 1 year. Drug abuse is a thus possible cause of severe extracerebral disabling vasculitis.

Pharmacokinetics of recombinant human erythropoietin in dialysis patients after single and multiple subcutaneous administrations.

The pharmacokinetics of recombinant human erythropoietin (rhEPO) were evaluated after single intravenous and single subcutaneous administration of 40 U/kg to 8 patients with dialysis treatment. All patients suffered from renal anemia with a hematocrit less than or equal to 24% and were treated with 40 U/kg rhEPO subcutaneously, three times a week for 6 weeks. At the end of the treatment period, kinetics of rhEPO were repeated. After the initial subcutaneous rhEPO dose, the following results were obtained: maximum plasma concentration 39.5 (26.7-56.9) U/l, area under the curve (AUC) 1,122 (582-3,220) U.h.1-1 and terminal half-life 13.2 (2.6-53.1) h. The corresponding data after multiple rhEPO doses were: maximum rhEPO plasma concentration 26.3 (9.4-49.1) U/l, AUC 724 (407-1,464) U.h.1-1 and terminal half-life 14.2 (3.5-24.4) h. There were no statistical significant differences between the two investigations. From the present study, it can be concluded that after a treatment period of 6 weeks with multiple subcutaneous rhEPO doses, rhEPO absorption as well as rhEPO elimination are unchanged.

Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients.

7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg.l-1) and trough levels (1.6 mg.l-1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2 beta) and during the haemodialysis session (t1/2 HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml.min-1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2 beta of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.

Multiple-dose-kinetics of ofloxacin after intraperitoneal application in CAPD patients.

Pharmacokinetics of ofloxacin in plasma and peritoneal fluid were studied in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Seven patients without peritonitis received 20 mg ofloxacin added to 2L dialysate i.p. every 6 h for one day only, while 4 patients with acute peritonitis were treated with this same dosage every 4 h for 3 days, then every 6 h for the next 7 days. Ofloxacin concentrations in plasma and dialysate were determined by HPLC. After i.p. drug application there was a rapid elimination of ofloxacin from dialysate, this being significantly faster in patients with peritonitis as compared to those without. Likewise, the total amount lost from the first bag after a 3 h dwell was higher in the peritonitis group (84.7 +/- 1.5%; mean +/- SEM) than in the non-peritonitis group (75.6 +/- 2.1%). Twenty-four h after start of ofloxacin treatment, the mean peritoneal fluid concentrations at the end of each exchange studied were all above 3 mg/L. In patients with peritonitis, plasma concentrations of ofloxacin rose to 0.94 +/- 0.05 mg/L after 24 h reaching a Cmax of 1.8 +/- 0.2 mg/L after a tmax of 84 +/- 23 h. Intraperitoneal administration of ofloxacin was well tolerated, and no local or systemic adverse events were observed. Peritonitis episodes that were caused by Staphylococcus epidermidis (3) and by E. coli (1) were cured in all patients.

Pharmacokinetics of ofloxacin and adequacy of maintenance dose for patients on haemodialysis.

Seven patients, three females and four males, aged 33-70 years, with end-stage renal disease, on regular haemodialysis were treated for various infections with a loading dose of 200 mg and multiple maintenance doses of 100 mg ofloxacin per 24 h over ten days orally. The pharmacokinetics of ofloxacin were studied at the end of the treatment period before, during and after a haemodialysis session. Concentrations in plasma and dialysate were measured by HPLC. Mean trough concentration (+/- S.D.) of ofloxacin before the last drug intake was 1.6 (+/- 0.6) mg/l. At a Tmax of 1.5 (+/- 1.1) h a peak concentration of 3.1 (+/- 1.0) mg/l was reached. The mean half-lives of ofloxacin (+/- S.D.) which were determined in the dialysis-free interval (T1/2 beta) and during the haemodialysis session (T1/2HD) were 38.5 (+/- 14.1) h and 9.9 (+/- 3.4) h, respectively. Mean dialyser clearance (+/- S.D.) was 59.2 (+/- 15.4) ml/min and the fractional removal of ofloxacin amounted to 21.5 (+/- 8.2)%. The data show that in patients with regular haemodialysis treatment a loading dose of 200 mg orally and daily administration of 100 mg orally of ofloxacin results in therapeutically favourable and well tolerated plasma concentrations when given at the end of haemodialysis.

Helium-cooled balloon-borne infrared experiment for measurements of stratospheric trace gas emissions.

A helium-cooled IR spectrometer with a diffraction-limited telescope was launched on 23 Sept. 1983 from Aire-sur-l'Adour (France) as part of the MAP/Globus 1983 campaign. The float altitude of the balloon was 38 km. Limb scan measurements of atmospheric emissions were taken in the 5.5-19-microm wavelength region. The measurements were performed ~1 h before sunrise. From several spectral features volume mixing ratios of NO(2), H(2)O, CH(4), HNO(3), O(3), and N(2)O were derived.

Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation?

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.

Antipyrine metabolite formation and excretion in patients with chronic renal failure.

In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.