Pharmacokinetics of long half-life antibacterials

Trimethoprim (TMP), sulfamethoxazole (SMZ) and sulfadiazine (SDZ) are characterized by elimination half-lives of 9 to 15 h. Effective serum concentrations can therefore be maintained by twice daily administration, but without a loading dose steady state levels will be reached only after 3 days. Renal disease has little effect on the pharmacokinetics of unchanged SMZ, whereas TMP and SDZ elimination is prolonged in uremia. Dosage adaptation to creatinine clearance is difficult, since the ratio of the two components in serum and urine will be altered. Abnormal drug accumulation in liver disease during a treatment with TMP and SMZ has not been demonstrate

Newer treatments for decompensated heart failure: focus on levosimendan

Acute heart failure (AHF) is a major cause of hospitalizations. Severe dyspnea, pulmonary congestion and low cardiac output with peripheral vasoconstriction and renal hypoperfusion is a main form of clinical presentation. Most patients with acute worsening have a pre-existing decompensated chronic heart failure (ADCHF), but AHF may also occur as a first manifestation of a previously unknown heart disease. Myocardial ischemia, cardiac arrhythmias, non-compliance with medication and infections are frequent precipitating factors. Management of AHF depends on the underlying heart disease and cause of decompensation. In patients with ADCHF vasodilators and iv diuretics are first-line drugs for rapid reduction of dyspnea and congestion. In patients with signs of low cardiac output and oliguria, inotropic agents are also often administered to prevent further deterioration. Beta-adrenergic agents and phosphodiesterase inhibitors correct the hemodynamic disturbance, but may also induce arrhythmias and worsen myocardial ischemia. Inotropic therapy therefore remains controversial. A novel class of drugs, the calcium sensitizers, represent a new therapeutic option. Levosimendan was shown to improve myocardial contractility without increasing oxygen requirements and to produce peripheral and coronary vasodilation. Its therapeutic effects and tolerance have been tested in several trials. The present review focuses on the clinical pharmacology and therapeutic utility of levosimendan in patients with ADCHF

European experience on the practical use of levosimendan in patients with acute heart failure syndromes

The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and post-interventional myocardial dysfunction (stunning) indicate that the inotropic and vasodilating actions of levosimendan may be of value in a wider range of indications. Dose recommendations, combination with other drugs, and potential side effects are discussed in this overview

Anthracycline-induced acute cardiotoxicity in adults treated for leukaemia: Analysis of the clinico-pathological aspects of documented acute anthracycline-induced cardiotoxicity in patients treated for acute leukaemia at the University Hospital of Zürich, Switzerland, bet ween 1990 and 1996

Background: Acute cardiotoxicity due to anthracyclines is a rare, but life-threatening event. Interindividual sensitivity to anthracyclines is highly variable and cannot be predicted for the individual patient. Patients and methods: This is a retrospective study. Medical charts and autopsy report of patients treated for acute leuke mia between 1990 and 1996 at the University Hospital of Zürich, Switzerland were reviewed and searched for anthracycline-associated acute cardiotoxicity. Patients with pre-existing heart disease known to be associated with cardiotoxicity were excluded. Results: Seven patients treated for leukemia with proven anthracycline-associated acute cardiotoxicity were included. In six patients the direct cause of death was acute cardiotoxicity due to the treatment. One patient recovered from cardiac failure but died a few months later from refractory leukemia. Clinical symptoms were those of a heart failure. Pathological findings were dilatative cardiac hypertrophy and pericardial effusion. Microscopically the typical findings of myocardial fibrosis and perinuclear vacuolisated myocytes were seen. Conclusions: The awareness of acute adverse effects on cardiac performance by anthracyclines faciliates early recognition and prevention of heart failure. Reliable tests are needed for the early diagnosis of subclinical myocardial damage in order to identify patients at ris

A soft X ray plane grating monochromator optimized for elliptical dipole radiation from modern sources

Abstract We describe a new but yet well proven way of making elliptically polarized dipole radiation from the BESSY II storage ring applicable to the SX700 type collimated plane grating monochromator PM3. We show that due to the limited vertical acceptance of the grating a simple use of vertical apertures is not possible in this case. Rather, deflecting the beam up or downwards by rotating the vertically collimating toroidal mirror M1 around the light axis leads to an excellent performance. The resulting detune of the photon energy can be taken into account by a readjustment of the monochromator internal plane mirror M2. The energy resolution of the beamline is not affected by the non zero roll of the collimating mirro

Plasma concentration monitoring of aminoglycosides

A narrow therapeutic margin and poor predictability of plasma concentrations are the main reasons for drug level monitoring during aminoglycoside treatment. Gentamicin, tobramycin, amikacin and netilmicin can now be accurately and rapidly measured by radioenzymic, radio-immuno and enzyme-immuno assays. Routine determinations of peak (1-2 h post dose) and trough levels are recommended to ensure adequate dosage in all patients with serious Gram-negative infections, especially when renal function is impaired. It should be realized, however, that maintaining aminoglycoside concentrations within a given range will only reduce, but not entirely eliminate the risk of toxicity. The pharmaco kinetic behaviour of these antibiotics leads to a progressive drug accumulation in renal tissue and the inner ear, which depends both on dosage amd duration of treatment. Une marge thérapeutique étroite ainsi que la difficulté a prédire les concentration plasmatiques, sont les principales raisons de contrôle des taux sanguins au cours d'un traitement par les aminoglycosides. Aujourd'hui les concentrations de gentamicine, tobramycine, amikacine et nétilmicine peuvent ětre mesurées rapidement et de manière précise par les méthodes radio-enzymatiques, radio immunologiques et enzymo-immunologiques. La détermination du pic (1 à 2 heures après administration) et du taux résiduel est recommandée pour assurer un dosage adéquat chez tous les malades atteints d'une infection sevère à germes Gram-négatif, et particulièrement en cas d'insuffisance rénale. Il faut pourtant bien garder à l'esprit, que le fait de maintenir la concentration d'une aminoglycoside à un niveau donné, permet seulement de diminuer les risques de toxicité, mais pas de les éliminer totalement. La pharmacocinétique particulière de ces antibiotiques entraine une accumulation progressive dans le parenchyme renal et dans l'oreille interne, qui depend à la fois de la posologie et de la durée du traitemen

Non-gapped Fermi surfaces, quasiparticles and the anomalous temperature dependence of the near-EFE_F electronic states in the CMR oxide La2−2x_{2-2x}Sr1+2x_{1+2x}Mn2_2O7_7 with x=0.36x=0.36

After years of research into colossal magnetoresistant (CMR) manganites using bulk techniques, there has been a recent upsurge in experiments directly probing the electronic states at or near the surface of the bilayer CMR materials La$_{2-2x}$Sr$_{1+2x}$Mn$_2$O$_7$ using angle-resolved photoemission or scanning probe microscopy. Here we report new, temperature dependent, angle resolved photoemission data from single crystals with a doping level of $x=0.36$. The first important result is that there is no sign of a pseudogap in the charge channel of this material for temperatures below the Curie temperature $T_C$. The second important result concerns the temperature dependence of the electronic states. The temperature dependent changes in the Fermi surface spectra both at the zone face and zone diagonal regions in $k$-space indicate that the coherent quasiparticle weight disappears for temperatures significantly above $T_C$, and that the $k$-dependence of the T-induced changes in the spectra invalidate an interpretation of these data in terms of the superposition of a `universal' metallic spectrum and an insulating spectrum whose relative weight changes with temperature. In this sense, our data are not compatible with a phase separation scenario.Comment: 6 pages, 4 figure

Band dependent emergence of heavy quasiparticles in CeCoIn5

We investigate the low temperature (T $<$ 2 K) electronic structure of the heavy fermion superconductor CeCoIn5 (T$_c$ = 2.3 K) by angle-resolved photoemission spectroscopy (ARPES). The hybridization between conduction electrons and f-electrons, which ultimately leads to the emergence of heavy quasiparticles responsible for the various unusual properties of such materials, is directly monitored and shown to be strongly band dependent. In particular the most two-dimensional band is found to be the least hybridized one. A simplified multiband version of the Periodic Anderson Model (PAM) is used to describe the data, resulting in semi-quantitative agreement with previous bulk sensitive results from de-Haas-van-Alphen measurements.Comment: 6 pages, 3 figure