Leishmaniosen im Kindesalter

Leishmaniosis is a protozoan infection that is acquired by the bites of sandflies. It is prevalent on all continents including various vacation areas for German tourists (e.g. Mediterranean countries and islands). Depending on the parasite species and strain as well as on the host immune response, the infection leads to papules or ulcers (cutaneous leishmaniosis) or to fever, hepatosplenomegaly and pancytopenia (visceral leishmaniosis). Diagnosis is made by the detection of the pathogen (histology, PCR and culture) in specialised laboratories. Unlike cutaneous leishmaniosis which requires a specific therapy only under certain conditions, visceral leishmaniosis must be treated. The drug of choice is liposomal amphotericin B. Despite successful treatment, later reactivation of the disease can occur during immunosuppression. There is no commercial vaccine available. The only prophylaxis is protection against sandfly bites.     

The safety profile of sustained release paracetamol during therapeutic use and following overdose.

Sustained release (SR) formulations of paracetamol (acetaminophen) have been introduced in several countries to provide lasting pain relief and reduced risk of rebound pain. However, few studies have evaluated the safety of paracetamol SR formulations.To assess the available published safety data regarding SR formulations of paracetamol, the EMBASE and MEDLINE databases were searched from 1980 to June 2003 for published worldwide human experience with paracetamol SR formulations. All publications that included any information about ingestion of any paracetamol SR formulation were systematically reviewed and abstracted by trained staff. The literature searches returned a total of 14 references containing safety data on paracetamol SR. In addition, the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers (AAPCC) database was searched for human exposure cases. The TESS database yielded 3003 cases from 1994 to 2002 that involved a paracetamol SR product.The available information indicates that the adverse event and safety profile of paracetamol SR is very similar to immediate release (IR) formulations of paracetamol. During therapeutic use, minor effects such as gastrointestinal upset and headache may occur. The rate of these effects varies substantially among studies but overall does not appear to be different between the SR and IR formulations of paracetamol. Overdose with paracetamol SR is expected to cause liver injury similar to overdose with IR formulations. The number of human exposure cases has increased since introduction of the SR formulation; however, sales of the SR formulation amounted to 7.5% of all paracetamol sales but accounted for 2.5% of the cases reported to poison centres. There were two deaths recorded in the TESS database: both were the result of multiple drug ingestion. No cases of death or unusual types of toxicity have been described from an overdose of paracetamol SR alone.     

Acute gastrointestinal bleeding: A comparison between variceal and nonvariceal gastrointestinal bleeding

Acute upper gastrointestinal bleeding (UGIB) is a typical medical emergency, with an incidence of 84 to 160 cases per 100,000 individuals and a mortality rate of approximately 10%. This study aimed to identify all cases of UGIB hospitalized in a tertiary gastroenterology department, to identify possible predictive factors involved in rebleeding and mortality, potential associations between different elements and the severity of bleeding, and the differences between the upper digestive hemorrhage due to nonvariceal and variceal bleeding. This was an observational, retrospective study of patients with UGIB admitted to the tertiary Department of Gastroenterology between January 2013 and December 2020. A total of 1499 patients were enrolled in the study. One thousand four hundred and ninety-nine patients were hospitalized for 7 years with active upper digestive hemorrhage, 504 variceal bleeding, and 995 nonvariceal bleeding. When comparing variceal with nonvariceal bleeding, in nonvariceal bleeding, the mean age was higher, similar sex, higher mortality rate, higher rebleeding rate, and higher hemorrhagic shock rate. Endoscopy treatment was also performed more frequently in variceal bleeding than in nonvariceal bleeding. Severe anemia was found more frequently in patients with variceal bleeding. The mortality rate was 10% in the entire study group, which was not significantly different between the 2 batches. However, the rebleeding rate is higher in patients with variceal gastrointestinal bleeding.     

Microbiologically Pure Cotton Fabrics Treated with Tetrabutylammonium OXONE as Mild Disinfection Agent

The microbiological purity of textiles plays a pivotal role in the use of textiles, especially in hospitals and other medical facilities. Microbiological purity of cotton fabric was achieved by a new disinfection method using tetrabutyloammonium OXONE (TBA-OXONE) before washing. As a result of the disinfection, the cotton fabric became microbiologically pure, despite the markedly decreased washing time with respect to the widely used standard procedure. Shortening of the washing time allowed for significant energy savings. In addition, the effect of the number of disinfection and washing cycles on the tensile properties and tearing force of the fabric was examined. After 120 disinfection and washing cycles the mechanical properties of cotton fabric were only slightly worsened.     

Spark Plasma Sintered Soft Magnetic Composite Based on Fe-Si-Al Surface Oxidized Powders

Soft magnetic composites (SMCs) need a stable matrix to apply heat treatments for enhancing their magnetic characteristics. A stable matrix can be offered by alumina, but the densification of the ferromagnetic particles covered by this oxide (by sintering) can be very difficult. This paper proposes a feasible synthesis route for obtaining alumina matrix SMCs. An Fe-Si-Al alloy with nominal composition Fe85Si9Al6 was obtained by mechanical alloying of elemental Fe, Si, and Al powders, and further, the as-milled powders were superficially oxidized by immersion in HCl solution. The oxide layer was composed of iron, silicon, and aluminum oxides, as the Fourier-transform infrared spectroscopy technique revealed. The Fe-Si-Al@oxide powder was densified by the spark plasma sintering technique—SPS. Upon sintering, a continuous matrix of oxide (mainly alumina) was formed by the reaction of the Fe-Si-Al powder coreswith their oxide layer. The main part of the composite compacts after sintering consisted of an Fe₃Si-ordered phase dispersed in an oxide matrix. The DC and AC tests of magnetic composite compacts showed that upon increasing the sintering temperature, the density, magnetic induction, and magnetic permeability increased. The initial magnetic permeability was constant in the entire range of testing frequencies and the magnetic losses increased linearly. The stability of the magnetic characteristics in frequency is promising for developing further such types of magnetic composite.     

Pharmacokinetics and comparative bioavailability of two vinpocetine tablet formulations in healthy volunteers by using the metabolite apovincaminic acid as pharmacokinetic parameter

The objective of this study was to evaluate the pharmacokinetics of apovincaminic acid, the main metabolite of vinpocetine ((3alpha, 16alpha) -eburnamenine-14-carboxylic acid ethyl ester, CAS 42971-09-5), and to assess the average bioequivalence of two immediate release formulations of 10 mg vinpocetine tablets in 24 healthy male volunteers. The relative bioavailability of the test (generic) product (Vimpocetina) with respect to the reference product was determined in a single dose, randomized, crossover study. A simple, rapid specific and reliable high performance liquid chromatographic method coupled with mass spectrometry detection has been developed and validated for vinpocetine and apovincaminic acid. However, only the concentrations of the metabolite could be used for bioequivalence determinations because the concentrations of the parent drug were too low to be accurately measured in the biological matrix. The compartmental analysis of the metabolite's appearance-disappearance in blood shows similarity with first-order kinetics of a drug extravascularly administered. The apparent pharmacokinetic constants were determined. The mean values for the Cmax were 49.5 (+/- 16) ng/ml for test and 51.4 (+/- 14) ng/ml for the reference product. The mean values for the AUC0-infinity were 95 (+/- 29) ng/ml x h for test and 96.9 (+/- 26) ng/ml x h for reference, respectively. The 90 % confidence intervals for test/reference mean ratios of the plasma pharmacokinetic variables Cmax and AUC0-infinity lie between 0.83-1.08 and 0.88-1.08, respectively, which is within the conventional bioequivalence range of 80-125 % (Schuirman test). The difference between Tmax of the test and reference products was statistically non-significant (Friedman test). The test product is therefore bioequivalent to the reference product with respect to the rate and extent of apovincaminic acid pharmacokinetics.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

Correction to: Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases -     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.