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

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

National survey on prescription of cardiovascular drugs among outpatients with coronary artery disease in Switzerland.

Secondary prevention of coronary artery disease markedly reduces cardiovascular mortality and non-fatal endpoints. Outpatient care of subjects with coronary artery disease has been assessed in several European countries, but no current data is available for Switzerland. A random sample of office-based physicians across Switzerland recorded current drug prescription of outpatients with coronary artery disease in the years 2000/2001 by means of a mail questionnaire. We assessed treatment frequencies according to different patient characteristics. 565 patients were included (mean age 68 +/- 11 years, 75% male). There was no evidence for differences in drug utilisation among the regions. Drug prescription rates for antithrombotic agents, beta-blockers, ACE-inhibitors/angiotensin receptor blockers and lipid lowering drugs were 91%, 58%, 50% and 63% respectively. Lower treatment rates were observed among patients >70 years and in those without a history of myocardial infarction or coronary revascularisation. Forty-nine percent of the patients had a blood pressure >140/>90, and 60% had lipid readings above the intervention cut-off according to the Swiss recommendations. Among those without a history of myocardial infarction or coronary revascularisation, the respective figures were 60% and 80%. Compared to former surveys evidence based drug prescription has improved in Switzerland. Despite this, therapeutic goals for cholesterol levels and blood pressure are not being reached in a large proportion of patients. A high risk group for under use of evidence based drugs are patients without a history of myocardial infarction or coronary revascularisation

Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation

Background: Malignancy is generally considered a contraindication for cardiac transplantation, whereas secondary malignancy has been described under chronic immunosuppression. Patients and methods: We report here the frequency of malignancy encountered among the 495 patients evaluated at our cardiac transplant centre as well as the incidence and the course of post-transplant malignancy among 129 consecutive patients who underwent cardiac transplantation, with a subsequent minimum follow-up of 6 months. Results: A total of 10 out of 495 patients (2%) evaluated for heart transplantation presented with a history of previous malignancy: 3 of them underwent transplantation (2 survive, 1 died) whereas in the remaining 7 patients neoplasia was considered a contraindication for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths). Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 ± 15 months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3 solid tumors). No significant association was found between post-transplant malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine antihuman T-cell monoclonal antibodies (OKT3). Conclusions: These results confirm that pre-transplant malignancy is not an absolute contraindication for cardiac transplantation and that post-transplant follow-up must include careful monitoring of post-transplant malignanc