Clinical and ultrasonographic correlations following three surgical anti-incontinence procedures (TOT,TVT and TVT-O)

The aim of this study was to compare ultrasonographic findings on tape position, angulation and mobility following three surgical anti-incontinence procedures (trans-obturator tape (TOT), tension-free vaginal tape (TVT), tension-free vaginal tape obturator (TVT-O)) and to correlate these data with clinical signs of cures and failures and de novo voiding disorders. In this prospective study, vesicourethral static and dynamic analysis of 81 patients (30 TOT, 28 TVT, 23 TVT-O) were evaluated using introital ultrasonography. Width, position and appearance of the tape were similar in all three groups, i.e. like a "V" at rest, round angulation on Valsalva and closed angulation at maximum retaining. Moreover, closer angulation on Valsalva was associated with voiding disorders. Closer angulation at retaining was associated with de novo urge incontinence. Larger angulation of the tape at rest appeared to be significantly associated with recurrent stress incontinence. Ultrasonography could a be useful tool assessing anti-incontinence procedures and investigating post-operative voiding disorders.     

Health values of patients with systemic sclerosis

OBJECTIVE: To assess health values in subjects with systemic sclerosis (SSc) and determine variability explained by demographics, clinical factors, health status, and disease severity. METHODS: We interviewed 107 individuals with SSc who attended national and local Scleroderma Foundation meetings in 2005. Health status was measured using the Short Form 36 (SF-36) Physical Component Summary (PCS; range 0-100) and Mental Component Summary (MCS; range 0-100), the Center for Epidemiologic Studies Depression Scale (CES-D; range 0-60), and the Health Assessment Questionnaire (HAQ) disability index (DI; range 0-3). Disease severity was assessed using a visual analog scale (VAS; range 0-150). Health value measures included the 0-100 health rating scale (RS), standard gamble (SG; range 0.0-1.0), and time trade-off (TTO; range 0.0-1.0). We performed univariate analyses to compare scores between participants with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), and multivariable analyses for 3 outcome measures: RS, SG, and TTO, controlling for demographics, type of SSc, health status, and disease severity. RESULTS: Of the 107 participants, 48 had dcSSc and 59 had lcSSc. Ninety-seven were women and 83 were white. The median scores for the PCS, MCS, and HAQ DI were 36.9, 45.5, and 0.9, respectively. Fifty-five subjects had significant depressive symptoms (CES-D score >or=16). The median RS, SG, and TTO scores were 62, 0.83 (indicating a willingness to accept up to a 17% risk of immediate death in exchange for perfect health), and 0.88 (indicating a willingness to give up a median of 12% of life expectancy in exchange for perfect health), respectively. Subjects with dcSSc had lower RS scores but higher SG scores (corresponding to a willingness to accept only a smaller risk of death) than subjects with lcSSc. TTO scores were similar in the 2 groups. Health values were variably related to factors such as demographics, VAS score, disease classification, and SF-36 PCS and MCS scores (R(2) = 0.22, 0.23, and 0.66 for the SG, TTO, and RS models, respectively). CONCLUSION: Individuals with dcSSc have lower health ratings but higher SG health values than individuals with lcSSc. These findings have implications for decision analysis and cost-effectiveness analysis.     

Bendamustine in non-Hodgkin lymphoma: the double-agent that came from the Cold War

Bendamustine was first synthesized in the early 1960s at the Institute for Microbiology and Experimental Therapy in Jena, East Germany by Ozegowski and Krebs. The molecule, originally termed IMET 3393 (4-[5-(bis[2-chloroethyl]amino)-1-methyl-2-benzimidazolyl] butyric acid), was intended to be a "bi-functional" molecule with alkylator and antimetabolite properties. Extensive studies were conducted using this compound over a 20-year period in East Germany, and it became a highly used chemotherapeutic agent in the eastern block before the fall of the Iron Curtain. After its licensing in Europe in the mid 1990s, more than 18,000 patients were studied using this compound, principally in Germany. Over the past decade, significant interest has been generated as a result of ongoing studies that have demonstrated the unique antitumor properties of this compound as a single agent and in different combinations. This article provides a review of studies using bendamustine in the treatment of non-Hodgkin lymphomas.     

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model

Purpose The objective of this study was to evaluate the anti-tumor efficacy and lack of systemic toxicity of paclitaxel when administered in pH-sensitive poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) nanoparticles in mice bearing human ovarian adenocarcinoma (SKOV-3) xenograft. Methods Paclitaxel-encapsulated PEO-modified PbAE (PEO–PbAE) nanoparticles were prepared by the solvent displacement method. PEO-modified poly(epsilon-caprolactone) (PCL) (PEO–PCL) nanoparticles were used as a non pH-responsive control formulation. Efficacy studies were conducted in SKOV-3 tumor-bearing athymic (Nu/Nu) mice at an equivalent paclitaxel dose of 20 mg/kg with the control and nanoparticle formulations. Safety of the drug when administered in the control and nanoparticle formulation was determined from blood cell counts and changes in body weight of the animals. Results The formulated paclitaxel-containing PEO–PbAE and PEO–PCL nanoparticles had a particle size in the range of 100–200 nm and a surface charge of + 39.0 and − 30.8 mV, respectively. After intravenous administration of paclitaxel in these formulations, the tumor growth was inhibited significantly. Both of the formulated nanoparticles tested have shown improved therapeutic efficacy as compared to the paclitaxel aqueous solution. Additionally, significantly lower toxicity profile of paclitaxel was observed with PEO-modified nanoparticles as compared to the aqueous solution formulation Conclusion PEO-modified PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced efficacy and safety profile in solid tumor therapy.     

Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery

Poly(ethylene glycol) (PEG)-modified thiolated gelatin (PEG-SHGel) anoparticles were developed as a long-circulating passively targeted delivery system that responds to intracellular glutathione concentrations to enhance DNA delivery and transfection. Reporter plasmid expressing enhanced green fluorescent protein (EGFP-N1) was encapsulated in the nanoparticles. DNA-containing gelatin (Gel) and thiolated gelatin (SHGel) nanoparticles were found to have a size range of 220 to 250 nm, whereas surface modification with PEG resulted in particles with a slightly larger size range of 310 to 350 nm. PEG modification was confirmed by electron spectroscopy for chemical analysis (ESCA), where an increase in the ether peak intensities of the C1s spectra corresponds to the surface presence of ethylene oxide residues. In addition, the PEG-SHGel nanoparticles released encapsulate plasmid DNA in response to varying concentrations of glutathione (up to 5.0 mM GSH in phosphate-buffered saline, or PBS). The stability of the encapsulated DNA was confirmed by agarose gel electrophoresis. Finally, from the qualitative and quantitative results of in vitro transfection studies in murine fibroblast cells (NIH3T3), PEG-Gel and PEG-SHGel nanoparticles afforded the highest transfection efficiency of the reporter plasmid. The results of these studies show that PEG-modified thiolated gelatin nanoparticles could serve as a very efficient nanoparticulate vector for systemic DNA delivery to solid tumors where the cells are known to have significantly higher intracellular GSH concentrations.     

Polymeric nano- and microparticle technologies for oral gene delivery

Gene therapy refers to local or systemic administration of a nucleic acid construct that can prevent, treat and even cure diseases by changing the expression of genes that are responsible for the pathological condition. Oral gene therapy has significant promise for treatment of local diseases such as inflammatory bowel disease and for systemic absorption of the expressed protein therapeutics. In addition, efficient oral delivery of DNA vaccines can have significant impact in disease prevention. The use of polymeric gene delivery vectors promises the translation of this experimental medical concept into clinical reality. This review addresses the challenges and opportunities in the development of polymer-based nano- and microparticle technologies for oral gene therapy. Specifically, the discussion is focused on different synthetic and natural polymers used for formulating nano- and microparticle technologies and the use of these delivery systems for oral DNA administration for therapeutic and vaccination purposes.