Neutral-pion photoproduction off protons in the energy range 0.3 GeV

Single pi(0) photoproduction has been studied with the CB-ELSA experiment at Bonn using tagged photon energies between 0.3 and 3.0 GeV. The experimental setup covers a very large solid angle of approximately 98% of 4pi. Differential cross sections dsigma/dOmega have been measured. Complicated structures in the angular distributions indicate a variety of different resonances being produced in the s channel intermediate state gammap-->N(*)(Delta(*))-->ppi(0). A combined analysis including the data presented in this letter along with other data sets reveals contributions from known resonances and evidence for a new resonance N(2070)D15.

Photoproduction of eta mesons off protons for 0.75 GeV

Total and differential cross sections for the reaction p(gamma,eta)p have been measured for photon energies in the range from 750 MeV to 3 GeV. The low-energy data are dominated by the S11 wave which has two poles in the energy region below 2 GeV. Eleven nucleon resonances are observed in their decay into peta. At medium energies we find evidence for a new resonance N(2070)D15 with (M,Gamma)=(2068+/-22, 295+/-40) MeV. At gamma energies above 1.5 GeV, a strong peak in the forward direction develops, signaling the exchange of vector mesons in the t channel.

Exophiala mesophila spec. nov.

In this paper a new fungus species, Exophiala mesophila Listemann et Freiesleben, is described. The species was isolated from silicone seals in the shower room of a hospital ward.

[Comparative susceptibility testing to sulfamethoxazole and trimethoprim by agar diffusion test on different media (author's transl)]. / Vergleichende Resistenzbestimmung gegen Sulfamethoxazol und Trimethoprim im Agar-Diffusionstest auf verschiedenen Nährmedien.

14 lots of 6 different commercial media for susceptibility testing were compared by agar diffusion test with 161 bacterial strains. The result "resistant" to sulfamethoxazole, trimethoprim, or co-trimoxazole varied in wide limits between the media. The lot employed by the "Work-Group on Resistance" of the Paul Ehrlich Society is of limited value for testing of the investigated drugs.

Antimicrobial agents in rats. I. Serum levels of parenteral cephalosporins.

Eleven cephalosporins were tested for their pharmacokinetic properties in rats in order to obtain a basis for experimental evaluation of their in vivo activity. The compounds were administered to female Wistar rats in i.m. doses of 150 or 50 mg/kg. The cephalosporin concentrations in rat serum were determined by the agar-well-diffusion method. Essential differences concerning the serum levels, half-life and the area under the curve could be ascertained. Low serum levels and short half-life could be reported for cephapirin, cephalotin, and cephradin, whereas cefazolin, cefazedone, and cefuroxime produced high and longer lasting serum levels. All cephalosporins were quickly absorbed, most of them were beneath the minimum detectable concentration after 6 h. It is concluded that pharmacokinetic data should be taken into consideration in conjunction with experimental chemotherapy.

Comparative assessment of cylacillin and ampicillin by experimental therapy and by serum level determinations in rats and mice.

Therapy of chronic E. coli pyelonephritis in rats was equally effective with cyclacillin and oral ampicillin, whereas intramuscular ampicillin had a significantly higher therapeutic activity than oral cyclacillin. Serum concentrations in rats and mice were consistently higher with cyclacillin than with ampicillin and showed great variations depending on the animal species. It was concluded that there is a good correlation between in vivo and in vitro activity of both antibiotics, provided that the serum levels are taken into consideration. On this basis it may be predicted that a man cyclacillin will exhibit lower therapeutic activity in gram-negative infections than ampicillin.

[Simultaneous therapy of gonorrhea with penicillin and probenecid. Serum penicillin picture]. / Simultane Gabe von Penizillin und Probenezid bei der Gonorrhöbehandlung. Untersuchungen von Penizillinserumspiegeln.

19 patient received penicillin and probenecid. The resulting serum concentrations of penicillin was determined. In regimen I 4 mill. IU depot penicillin was given i.m. simultaneously with 1 g probenecid orally. In regimen II probenecid was given 30 min prior to the administration of penicillin. In both series the average serum concentrations of penicillin were not significantly different (p = 0.01).

Antimicrobial agents in rats. II. Serum levels of oral cephalosporins.

Cephalexin, cephradine and 7 beta-(D-2-amino-2-[(1,4-cyclohexadienyl)-acetamido])-3-methoxy-3-cephem-4-carboxylic acid (CGP 9000) were tested for their pharmacokinetic behaviour in rats. The cephalosporin serum concentrations were determined at certain times after oral administration of 150 mg/kg by the agar-well-diffusion method. The experiments revealed that the serum levels of cephalexin and cephradine did not differe essentially from one another. They maintained maximum serum concentrations of 30 microgram/ml to 40 microgram/ml during the first hour and than declined with a half-life of 2.5 h. CGP 9000 reached peak concentrations 60 to 90 min postdose and was eliminated with a half-life of 3.5 h. The area under the curve was double as large as those of cephalexin and cephradine. This may be a reason of favourable results in experimental chemotherapy with CGP 9000.

[Therapeutic studies on two different models of experimental pyelonephritis (author's transl)]. / Therapiestudien an zwei Pyelonephritismodellen mit differenter Infektbahnung.

By transurethral instillation of a suspension of a serum resistant E. coli strain (serotype O25:19:12), chronic pyelonephritis is induced in rats, if systemic and local defense mechanisms are impaired by estradiol application. Without hormonal treatment a similar infection can be achieved with a more virulent E. coli strain (serotype O2:1:4). Due to the chronic course of the renal infection in either model, beginning of therapy may be delayed (e.g., 10 days after infection) thus imposing difficult therapeutic conditions on the efficacy of antibiotics to be tested. Evaluation of antibiotics in both models produced differential therapeutic results. In spite of equal MIC's for the applied E. coli strains, gentamicin and particularly cefazolin treatment was less effective in the estradiol treated rats than in those without hormone application. Cefuroxime therapy produced favourable results in either model. The different therapeutic efficacy in both models is to be explained by differences in host resistance to infection. It is suggested that by simultaneans testing of antibiotics in either model, it will be possible to estimate to what extent the therapeutic efficacy of antibiotics depends on the support of intact host defense mechanisms.

[Netilmicin and tobramycin: comparative evaluation of pharmacokinetics, nephrotoxicity, and therapeutic efficacy in animal studies (author's transl)]. / Netilmicin und Tobramycin: vergleichende tierexperimentelle Untersuchungen zur Pharmakokinetik, Nierenverträglichkeit und therapeutischen Effektivität.

Pharmacokinetics, nephrotoxicity, and therapeutic efficacy of (2S-cis)-4-O-[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]-2-deoxy-6-O-[3-deoxy-4-C-methyl-3-(methyl-amino)-beta-L-arabinopyranosyl]-N1-ethyl-D-streptamine sulfate (netilmicin) and tobramycin were investigated in rats. The excretion rates of tubular cells and of the urinary enzyme malic dehydrogenase served as parameter of nephrotoxicity. Both compounds were, similar to other aminoglycosides, tubulotoxic within the range of dosages used for human therapy. Netilmicin, however, produced less renal damage than did tobramycin in all dosages applied. Pharmacokinetic studies revealed lower renal concentrations of netilmicin after repetitive administration. Experimental chemotherapy of the chronic E. coli pyelonephritis in rats with both aminoglycosides resulted in a significant reduction of the renal bacterial counts. In spite of approximately identical serum concentration curves and in vitro activity, especially the low dosage of netilmicin led to more favourable therapeutic results than equal doses of tobramycin. These animal experiments suggest higher renal tolerance and efficacy of netilmicin.

Investigations on the effectiveness of cefazedone in experimental E. coli pyelonephritis.

The therapeutic effectiveness of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephazolin, cephacetrile and cephalothin was compared in the test model of estradiol-induced E. coli pyelonephritis in the rat. Cefazedone and cephazolin were similar in effect. The relations between results of treatment and microbiological and pharmacokinetic characteristics of the cephalosporins tested are discussed.

[Antibacterial in-vitro activity of pipemidic acid and nalidixic acid (author's transl)]. / Antibakterielle In-vitro-Wirksamkeit von Pipemidsäure und Nalidixinsäure. Vergleichende Untersuchungen.

The in-vitro activity of nalidixic acid and pipemidic acid was investigated in a combined study in 450 freshly isolated bacterial strains using the agar dilution test. Gram-positive cocci were resistant to both substances except for a few pipemidic acid sensitive staphylococci. Both substances had good antibacterial activity in the gram-negative spectrum. However, the MIC values of pipemidic acid were generally clearly lower than those of nalidixic acid. Only pipemidic acid showed activity against Pseudomonas aeruginosa. Thus the in-vitro results showed that pipemidic acid has clear-cut and valuable advantages for the treatment of urinary tract infections when compared with nalidixic acid.

[The differentiation of potential nephrotoxicity of various aminoglycosides in animal experiments]. / Die Differenzierung der potentiellen Nephrotoxizität verschiedener Aminoglykoside im Tierexperiment.

Experimental differentiation in the animal of nephrotoxicity of various aminoglycosides. Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin were demonstrable by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect-relationships were found resulting in reproducible different toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed by their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycosides than with gentamicin in order to avoid renal damage.

[Animal experiment studies on the question of damage to the fetal kidney by gentamycin]. / Tierexperimentelle Untersuchungen zur Frage einer Schädigung der fetalen Niere durch Gentamyzin.

It is reported about animal experiments of pregnant guinea pig. We found a special affinity of gentamyzin to maternal and fetal kidney-tissue. The application of this aminoglycosid seems therefore problematic in pregnancy.

[Side effects of aminoglycosides: nephrotoxicity (author's transl)]. / Nebenwirkungen von Aminoglykosiden: Nephrotoxizität

Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in the tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin can be demonstrated experimentally by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect relationships were established resulting in varying reproduceable toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed in their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycerides than with gentamicin in order to avoid renal damage.

Ceftazidime, ceftizoxime, cefotaxime and HR 221 in experimental chronic Escherichia coli pyelonephritis in rats.

The therapeutic efficacy and pharmacokinetics of the cephalosporins ceftazidime, ceftizoxime, cefotaxime and HR 221 were studied in animal experiments. The animal model used was experimental estrogen-induced or non-induced chronic Escherichia coli pyelonephritis in rats. The animals were treated with 5 mg cephalosporin/kg twice daily for one week. Each of the cephalosporins tested led to a significant decrease in renal bacterial counts, in spite of the low doses given. Ceftazidime was significantly more active than HR 221 in both experimental models, although the serum levels of HR 221 were higher and were maintained for a longer period of time than those of ceftazidime. Differences in pharmacokinetic properties (influenced by metabolic stability and protein binding) could be the reason for the differences in therapeutic activity, since the in vitro antimicrobial activity of each of the cephalosporins tested was very similar against the test strain.

[Resistance of Haemophilus influenzae to antibiotics in the Federal Republic of Germany (author's transl)]. / Antibiotikaresistenz von Haemophilus influenzae in der Bundesrepublik Deutschland.

In a multi-center study 523 strains of H. influenzae and H. parainfluenzae isolated from patients in eight towns of the Federal Republic of Germany were tested for their sensitivity to 15 different chemotherapeutic agents. 1.7% of the strains were resistant to ampicillin, 1,5% to chloramphenicol and 2.5% to tetracycline. All ampicillin-resistant strains produced beta-lactamase. For the first time, multiple resistant strains were isolated: two against ampicillin, chloramphenicol and tetracycline; one in addition also against co-trimoxazole. It is likely that there will be a spread of such resistant strains.