Ultrahigh-energy cosmic rays: physics and astrophysics at extreme energies.

The origin of cosmic rays is one of the major unresolved questions in astrophysics. In particular, the highest energy cosmic rays observed have macroscopic energies up to several 10(20) electron volts and thus provide a probe of physics and astrophysics at energies unattained in laboratory experiments. Theoretical explanations range from astrophysical acceleration of charged particles, to particle physics beyond the established standard model, and processes taking place at the earliest moments of our universe. Distinguishing between these scenarios requires detectors with effective areas in the 1000-square-kilometer range, which are now under construction or in the planning stage. Close connections with gamma-ray and neutrino astrophysics add to the interdisciplinary character of this field.

Effect of probenecid on the distribution and elimination of ciprofloxacin in humans.

OBJECTIVE: Probenecid-sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers. METHODS: A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (M1) by reversed-phase HPLC. RESULTS: Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume of distribution did not differ significantly with and without coadministration of probenecid. Peak plasma concentration, plasma area under the concentration-time curve, and elimination half-life of M1 were increased (p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma. CONCLUSIONS: Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug-drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.

Fleroxacin versus ofloxacin in patients with complicated urinary tract infection: a controlled clinical study.

This prospectively randomized study compared fleroxacin, 400 mg once daily, with ofloxacin, 200 mg twice daily, administered orally for 7-14 days for the treatment of complicated urinary tract infection (UTI) in hospitalized, urologic patients. A total of 80 patients were enrolled in the study. Of these, 30 patients treated with fleroxacin and 35 treated with ofloxacin could be evaluated for therapeutic efficacy. Of the causative organisms, 29 of 30 in the fleroxacin group and 33 of 35 in the ofloxacin group were eliminated. One relapse occurred in the fleroxacin group and two in the ofloxacin group. Reinfection with gram-positive isolates was seen in five patients treated with fleroxacin and in one treated with ofloxacin. Thus, the cure rate was 24 (80%) of 30 in the fleroxacin group and 32 (91%) of 35 in the ofloxacin group. In general, both antibiotics were well tolerated. Four patients in the fleroxacin group and five in the ofloxacin group claimed mild, possibly drug-related adverse effects. The treatment of one patient in the ofloxacin group had to be discontinued because of an adverse effect (headache). Both fleroxacin and ofloxacin are effective and well-tolerated antibiotics for the treatment of complicated UTI.

Effect of prolonged sedation with propofol on serum triglyceride and cholesterol concentrations.

We compared changes in serum lipid concentrations in ICU patients receiving a 3-day continuous infusion of propofol with those in patients receiving conventional sedation. No adverse effects were observed and the serum lipid concentrations were not significantly influenced by propofol. It is concluded that propofol might be a suitable agent for long-term sedation in the ICU, although serum lipid concentrations should be monitored throughout its administration.

On the prognosis of IDDM patients with large kidneys.

BACKGROUND: Approximately 10-30% of IDDM patients develop diabetic nephropathy depending on the metabolic control. Previous examinations on the significance of the kidney size prior to the manifestation of nephropathy produced varying results. METHODS: The present study, therefore, was designed to assess the correlation between sonographically determined kidney size and kidney function over 8 years in a follow-up examination, and to evaluate a potential risk pattern. Data could be collected from 73 (66%) of 110 IDDM patients with initially normal serum creatinine whose sonographically determined kidney volume (cm3 = L cm x W cm x D cm x pi/6) and kidney function (creatinine, albuminuria, beta2-microglobulin in serum) had been examined in 1986, and who had a diabetes duration of 1 month to 25 years at that time. RESULTS: 30% (11 of 37) patients with large kidneys (>170 cm3) reached at least one serious renal end-point (increase of serum creatinine by more than 50%, requirement of dialysis or kidney transplantation, or death in end-stage renal disease) versus one of 36 patients with normal kidney size (P<0.002). As many as 42% of patients with large kidneys developed abnormal creatinine values (>106 micromol/l) in contrast to only 20% of the patients with normal kidney volume (P<0.05). Six of seven patients with a more than 50% increase of serum creatinine from baseline showed large kidneys in 1986, but had a normal serum creatinine, and four also a normal urine albumin excretion. Furthermore all five patients with more severe end-points (two deaths in end-stage renal disease and three patients presently requiring dialysis) exhibited either an increased serum creatinine or large kidneys at baseline; four of these, however, were still in the normoalbuminuric state in 1986. CONCLUSIONS: These results indicate that large kidneys might be a morphological marker for subsequent diabetic nephropathy, and as a consequence, renal insufficiency.

Is iron oxide a tissue-specific contrast medium in diagnostic ultrasound? A case report.

We present a patient with Hodgkin's disease in whom computed tomography suggested focal lesions in the liver. As no lesions were detected by diagnostic ultrasound, magnetic resonance imaging (MRI) with iron oxide as contrast medium was performed for verification. MRI confirmed at least 3 small lesions. The ultrasound study performed immediately after this MRI scan easily detected these lesions. A biopsy was taken and histology showed infiltrates of Hodgkin's disease. The change in echogenicity of the liver and/or the lymphomatous tissue may be an effect of iron oxide. This observation has not been reported before.

Relative bioavailability of three cefixime formulations.

Three galenic formulations of cefixime (tablet, syrup and dry suspension) containing 200 mg each were compared with respect to their relative bioavailability in twelve healthy volunteers. All three formulations showed reliable absorption. Mean peak plasma concentrations were reached after 3.3-3.5 h, mean terminal half lives were 2.9-3.1 h. 18-24% of the dose administered were recovered unchanged in the urine. Best bioavailability was obtained with the dry suspension (AUC0-infinity = 25.8 +/- 7.0 micrograms/ml h; Cmax = 3.4 +/- 0.9 microgram/ml), followed by the tablet (AUC0-infinity = 20.9 +/- 8.1 micrograms/ml h; Cmax = 3.0 +/- 1.0 micrograms/ml) and the syrup which is based on triglycerides (AUC0-infinity = 17.8 +/- 5.9 micrograms/ml h; Cmax = 2.4 +/- 0.7 micrograms/ml). The statistical analysis resulted in bioinequivalence between dry suspension and syrup. It is concluded that best bioavailability of cefixime after oral administration is guaranteed when taken in an "aqueous medium" either as dry suspension or as tablet with "plenty of liquid".

Implications of a possible clustering of highest-energy cosmic rays.

Recently, a possible clustering of a subset of observed ultra-high energy cosmic rays above approximately 40 EeV (4 x 10(19) eV) in pairs near the supergalactic plane was reported. We show that a confirmation of this effect would provide information on the origin and nature of these events and, in case of charged primaries, imply interesting constraints on the extragalactic magnetic field. Possible implications for the most common models of ultra-high energy cosmic ray production in the literature are discussed.

[Enoxacin concentration in seminal fluid, in prostate secretions and in prostatic adenoma tissue following oral administration or intravenous infusion]. / Enoxacin-Konzentrationen in der Samenflüssigkeit, im Prostatasekret und im Prostataadenomgewebe nach oraler Gabe oder intravenöser Infusion.

In eleven volunteers and 39 patients undergoing transurethral resection of the prostate or bladder tumor, concentrations of enoxacin were measured in seminal fluid (volunteers), in prostatic fluid (volunteers, patients) and in prostatic adenoma tissue (patients) after oral (400 mg) administration and intravenous (428 mg) infusion (60 min) of enoxacin. Simultaneously 2.534 g of iothalamic acid was i.v. injected to identify possible urinary contamination. The concentrations of enoxacin in seminal fluid after 2-4 h and in prostatic tissue after about 1-4 h and 14-16 h exceeded plasma concentrations more than two-fold. The concentrations in prostatic fluid after 1-4 h were about half the plasma concentrations. Venous blood samples were taken after intravenous infusion at intervals of up to 24 h in a total of 14 patients. The mean plasma concentration of enoxacin decreased from its maximum of 6.9 mg/l at the end of infusion to 0.5 mg/l at 12 h after administration. A terminal half life of 6.65 h was calculated according to an open two-compartment model.