Subtoxic cell responses to silica particles with different size and shape.

Health risks from particles are a priority challenge to health protection at work. Despite the ubiquitous exposure to a wide range of particles and the many years of research in this field, there are fundamental unresolved questions regarding the prevention of particle-related respiratory diseases. Here, the highly relevant particulate material silicon dioxide was analyzed with emphasis on defined size and shape. Silica particles were prepared with different size and shape: Spheres (NS nanospheres 60 nm; SMS submicrospheres 230 nm; MS microspheres 430 nm) and rods (SMR submicrorods with d = 125 nm, L = 230 nm; aspect ratio 1:1.8; MR microrods with d = 100 nm, L = 600 nm; aspect ratio 1:6). After an in-depth physicochemical characterization, their effects on NR8383 alveolar macrophages were investigated. The particles were X-ray amorphous, well dispersed, and not agglomerated. Toxic effects were only observed at high concentrations, i.e. ≥ 200 µg mL-1, with the microparticles showing a stronger significant effect on toxicity (MS≈MR > SMR≈SMS≈NS) than the nanoparticles. Special attention was directed to effects in the subtoxic range (less than 50% cell death compared to untreated cells), i.e. below 100 µg mL-1 where chronic health effects may be expected. All particles were readily taken up by NR8383 cells within a few hours and mainly found associated with endolysosomes. At subtoxic levels, neither particle type induced strongly adverse effects, as probed by viability tests, detection of reactive oxygen species (ROS), protein microarrays, and cytokine release (IL-1ß, GDF-15, TNF-α, CXCL1). In the particle-induced cell migration assay (PICMA) with leukocytes (dHL-60 cells) and in cytokine release assays, only small effects were seen. In conclusion, at subtoxic concentrations, where chronic health effects may be expected, neither size and nor shape of the synthesized chemically identical silica particles showed harmful cell-biological effects.

Bendamustin-Rituximab Combination Is a Safe and Effective, Ambulatory Treatment for Elderly Patients with Chronic Lymphocytic Leukemia: Retrospective Real-world Analysis by Age from a German Registry and Review of the Literature.

BACKGROUND: Treatment recommendations in chronic lymphocytic leukemia (CLL) are based upon selected, otherwise healthy study populations mostly under 72 years of age. The Project group Internistic Oncology (PIO) embarked on an analysis of the 'real-world' safety and efficacy of bendamustine with and without rituximab in unselected outpatients. PATIENTS AND METHODS: A multicenter, open-label, prospectively stratified, retrospective study was conducted to determine routine feasibility, toxicity, and response rates obtained by bendamustine with and without rituximab in a random population of mostly elderly patients with CLL. Records were obtained from 775 patients with CLL from 60 private medical oncology practices. Informed consent was obtained prior to study participation. The median observation time was 28 months. Patients were stratified according to age, and treatment. Response criteria and statistics followed international guidelines adopted by the "German Chronic Lymphocytic Leukemia Study Group". RESULTS: Overall, 57.5% of patients were over 70 (range=36-95) years old. Eastern Cooperative Oncology Group performance status and age influenced the total dose given, decreasing by 20% between ECOG 0 and 3, and by 15% above 80 years old. Response rates did not differ between the ages of 60 to 80 years, with an overall remission rate for bendamustine of 83%, and for the combination therapy of 89%, decreasing above the age of 80 years. Febrile neutropenia occurred in 25% of 775 patients, and grade 3 or 4 non-hematological adverse events in 9.55% (n=74), not interfering with the treatment. CONCLUSION: Bendamustine with and without rituximab was associated with high activity and tolerability, irrespective of age and risk factors. The median overall survival was 64 months with a 3-year survival rate of 72%; progression-free survival was 30.6 months, and the 3 year PFS was 43%. The good tolerability and feasibility of bendamustine with and without rituximab, in particular for the elderly population with CLL argues for it being a safe outpatient treatment.

[Centralized biobanks: a basis for medical research]. / Zentralisierte Biobanken als Grundlage für die medizinische Forschung.

Biobanks are the basis for a substantial part of biomedical research. The development, establishment and operation of biobanks are connected to a broad range of aspects, mainly concerning the preparation, storage, usage and dissemination of samples and associated data, in addition to the social and public involvement of these processes. These complex requirements can often only be managed in large centralized biobanks. In recent years, centralized clinical biobanks have been established in several university clinics in Germany. Similar activities take place in other European countries and worldwide. This article highlights the requirements and main tasks of centralized clinical biobanks: high-quality pre-analytics and sample storage, the creation of professional IT structures, data protection, ethical issues, in addition to quality and project management.

Drug-disease interaction in elderly patients in family practice.

OBJECTIVE: To determine the frequency of potential drug-disease interaction in elderly patients in family practice. To assess which drugs and diagnoses are associated with a high risk related to drug-disease interaction and whether there are gender- or age-related differences. METHODS: In routinely recorded electronic patient records, patients at least 65 years old with at least one diagnosis named in Beers list and one prescription were identified. Potential drug-disease interaction (PDDI) was presumed if within the same 3 months a "Beers" diagnosis and a potentially inappropriate prescription with respect to this diagnosis were documented for a patient. Multiple logistic regression analysis identified factors associated with a high risk of PDDI. RESULTS: Of 24,619 patients (63.4% women) corresponding to our inclusion criteria, 10.4% were exposed to at least one PDDI. Almost no (0.0%) PDDI was associated with the most common Beers disorder hypertension (prevalence 49.2%). However, 23.4% of men suffering from bladder outflow obstruction (prevalence 17.6% in males) were exposed to at least one PDDI. PDDI was quite common in some rarer conditions, for example, indications for anticoagulation (prevalence 2.6%, 31.5% PDDI). PDDI was not influenced by gender, but associated with taking more than 4 drugs (OR 1.91 (1.83 - 2.00)), suffering from more than one Beers disorder (OR 1.24 (1.16 - 1.31)), and advanced age (OR 1.10 (1.05 - 1.15)). CONCLUSIONS: High risk patient groups could be identified. Some disorders as well as some drugs are particularly prone to risky constellations; these should be reflected in systems assisting prescribing with regard to patient safety.

[Frequency of dizziness-related diagnoses and prescriptions in a general practice database]. / Diagnosehäufigkeiten und Verordnungen bei Schwindel im Patientenkollektiv einer hausärztlichen Routinedatenbank.

INTRODUCTION: Dizziness can be due to multiple causes. However, the aetiology often remains unclear. At the same time, there is a lack of evidence-based treatment options. The aim of this study was to investigate the frequency of dizziness-related diagnoses, referrals and prescriptions in a general practice database. METHODS: Data from computerized patient records of 138 general practices participating in the MedViP project were used for cross-sectional analysis of the time period April 2001 until December 2002. The identification of dizzy patients was performed via ICD-10 diagnoses, free text fields and medication issued for dizziness. Frequencies were counted and odds ratios calculated to describe associations between diagnoses and medication. RESULTS: For the period of investigation, 10,971 patients (from a total of 317,042 documented patients) were given at least one diagnosis of dizziness (prevalence 3.4%; mean age 59 years, 67.2% female). In 80.2% of the cases dizziness was coded as a symptom (R42) rather than a discrete disease. Prescriptions for dizziness were rather uncommon. An analysis of ATC codes showed that 6.6% of all affected patients were prescribed a specific drug for dizziness, most frequently betahistine. Antiemetics were prescribed in 7.1%, and the homeopathic preparation "Vertigoheel" in 2.8% of the dizzy patients. Betahistine was significantly more often prescribed for "unspecified" dizziness, vestibular neuritis, and benign paroxysmal positional vertigo; but not for Meniere's disease. It was given less often in "other peripheral" and in central vertigo as well as in cases where the symptom was coded (R42). 3.9% of the dizzy patients had been referred to the neurologist (55.4%), ENT-specialist (30.5%) or to both specialists (14.1%). CONCLUSIONS: The manner of coding and prescribing reflects both a symptom-orientated classification used by general practitioners and the limitation of treatment options.