Amphiphilic and biodegradable hy-PEI-g-PCL-b-PEG copolymers efficiently mediate transgene expression depending on their graft density

Novel biodegradable amphiphilic copolymers hy-PEI-g-PCL-b-PEG were prepared by grafting PCL-b-PEG chains onto hyper-branched poly(ethylene imine) as non-viral gene delivery vectors. Our investigations focused on the influence of graft densities of PCL-b-PEG chains on physico-chemical properties, DNA complexation and transfection efficiency. We found that the transfection efficiencies of these polymers increased at first towards an optimal graft density (n=3) and then decreased. The buffer-capacity-test showed almost exactly the same tendency as transfection efficiency. Cytotoxicity (MTT-assay) depended on the cooperation of PEG molecular weight and graft density of PCL-b-PEG chains. With increasing the graft density, cytotoxicity, zeta-potential, affinity with DNA, stability of the polyplexes and CMC-values were reduced strongly and regularly. Increasing the excess of polymer over DNA was shown to result in a decrease of the observed particle size to 100-200 nm.     

Conservative management of symptomatic Carpal Bossing in an elite hockey player: a case report

Objective:

To present the characteristics and create awareness of symptomatic carpal bossing and discuss potential etiologies and the role of conservative management through the presentation of an athlete with traumatic onset of symptomatic carpal bossing.

Clinical features:

This case report outlines the presentation and conservative management of an elite eighteen year old hockey player with symptomatic carpal bossing after a traumatic on ice collision. Carpal bossing is a bony, dorsal prominence in the quadrangular joint of the wrist that is inconsistently symptomatic.

Intervention and outcome:

A conservative treatment plan consisting of education, reassurance, avoidance of aggravation, and soft tissue therapy allowed return to play in two weeks without restrictions or need for surgical consultation.

Conclusion:

With inconsistent recurrence rates and surgical complications, the role of conservative management for symptomatic carpal bossing deserves further exploration. The conservative practitioner should be aware of the signs and symptoms of symptomatic carpal bossing to institute suitable treatment.     

An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy

To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower spinal muscular atrophy functional rating scale (SMAFRS) scores and were more likely to be non‐ambulatory. There was, however, no difference between the groups in quantitative muscle strength or pulmonary function testing. Functional scale may be a more discriminating outcome measure for SMA clinical trials. Muscle Nerve, 2009     

Pharmaceutical care for patients with ischemic stroke: improving the patients quality of life

Objectives To improve patients health-related quality of life (HQL) after transient ischemic attack (TIA) or ischemic stroke; to guarantee an effective secondary prevention; to increase the patient’s satisfaction with recommendations regarding their medication by pharmacists. Setting Stroke Unit, neurological ward at the Klinikum Fulda, rehabilitation hospitals and community-based pharmacies in the region of Fulda, Germany. Method Patients with TIA or ischemic stroke were included. The patients were assigned to an intervention group (IG) or a control group (CG). The individual assignment of patients to IG or CG was based on the type of the local pharmacy to which patients belong. Community-based pharmacies either delivered standard care (CG) or provided additional intensified pharmaceutical care (PC; IG). Pharmacies delivering PC belong to a pre-existing “Quality Assurance Working Group” (QAWG). To evaluate the patient’s HQL, the Short Form-36 (SF-36) was used at study entry in hospital and at 12 months. The secondary prevention was documented at study entry in hospital and at 12 months. The patients’ satisfaction was measured by a questionnaire at the end of the study. Main outcome measures Patients’ HQL; secondary prevention; patients’ satisfaction with recommendations of the pharmacists with regards to their medication. Results Out of 1316 patients screened for participation in this study, 255 were recruited with 90/255 patients assigned to the IG and 165/255 patients assigned to the CG. During the study, the HQL of the patients in the IG did not change significantly. A significant decrease in the HQL was observed for the CG in 7/8 subscales and in both summary measures of the SF-36. After 12 months, 85.3% of the patients in the IG and 86.3% of the patients in the CG were treated with antiplatelet drugs or oral anticoagulants in accordance to treatment guidelines. Patients in the IG were significantly more satisfied with the individualized recommendations of the pharmacists than patients in the CG. Conclusion Our findings indicate that an intensified PC of patients after ischemic stroke by dedicated pharmacists may have a positive impact on HQL and patients’ satisfaction. PC in this study had no impact on adherence to secondary prevention medication.     

Brush-like branched biodegradable polyesters, part III. Protein release from microspheres of poly(vinyl alcohol)-graft-poly(D,L-lactic-co-glycolic acid).

Brush-like branched polyesters, obtained by grafting poly(lactic-co-glycolic acid), PLGA, onto water-soluble poly(vinyl alcohol) (PVAL) backbones, were investigated regarding their utility for the microencapsulation of proteins. Poly(vinyl alcohol)-graft-poly(lactic-co-glycolic acid), PVAL-g-PLGA, offers additional degrees of freedom to manipulate properties such as e.g. molecular weight, glass transition temperature and hydrophilicity. PLGA chain length was varied at a constant molecular weight (M(w)) of the PVAL backbone and secondly M(w) of the PVAL backbone was varied keeping the PLGA chain lengths constant. The most striking feature of these polymers is their high M(w). Microencapsulation of hydrophilic macromolecules, such as bovine serum albumin, ovalbumin, cytochrome c and FITC-dextran using a w/o/w double emulsion technique was investigated. Surface morphology, particle size, encapsulation efficiencies and protein release profiles were characterized as well. Microencapsulation of model compounds was feasible at temperatures of 0-4 degrees C with yields typically in the range of 60-85% and encapsulation efficiencies of 70-90%. Both, encapsulation efficiency and initial protein release (drug burst) were strongly affected by the glass transition temperature, T(g), of the polymer in contact with water, whereas the in vitro protein release profile depended on the PVAL-g-PLGA structure and composition. In contrast to PLGA, protein release patterns were mostly continuous with lower initial drug bursts. Shorter PLGA chains increased drug release in the erosion phase, whereas initial pore diffusion was affected by the M(w) of PVAL backbone. Release profiles from 2 to 12 weeks could be attained by modification of composition and molecular weight of PVAL-g-PLGA and merit further investigations under in vivo conditions. The in vitro cytotoxicity of PVAL-g-PLGA is comparable to PLGA and therefore, this new class of biodegradable polyesters has considerable potential for parenteral drug delivery systems.     

Case-of-the-month: painful thigh mass in a young woman: diabetic muscle infarction.

A 29-year-old female with type I diabetes mellitus developed pain, focal tenderness, and swelling in the posterior left thigh. Subsequent evaluation included a muscle biopsy, which revealed large confluent areas of necrosis and edema, compatible with a diagnosis of diabetic muscle infarction (DMI). Diabetic muscle infarction (DMI) is an unusual neuromuscular complication of diabetes mellitus. DMI begins with the acute onset of focal pain and swelling in the thigh. The anterior compartment (quadriceps muscle group) or posterior compartment (hamstring muscle group) are most frequently involved. The focal region of muscle damage can be noninvasively viewed by magnetic resonance imaging and radionuclide scans. Muscle biopsy demonstrates large confluent regions of muscle necrosis and edema. DMI needs to be differentiated from other processes that can cause leg pain in a diabetic patient.