Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT^®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel.     

Myositis ossificans progressiva and pregnancy. A therapeutic dilemma

Myositis ossificans progressiva is a rare but progressively debilitating autosomal dominant disease characterized by extraskeletal ossification involving muscle connective tissue. This report is the first on pregnancy and induced abortion in a patient with myositis ossificans progressiva. Intraoperative sector scanning ultrasound was of limited benefit in evacuation of the uterine cavity. Conservative management of an incomplete termination resulted in no adverse sequelae.     

A new technique to overcome failed second-trimester amniocentesis due to membrane tenting

Membrane tenting during amniocentesis is a significant cause of dry taps, leading to immediate procedure failure or multiple needle insertions. Because of the increased risk of fetal loss and other minor complications reported with multiple taps, a means of accomplishing fluid retrieval on a single pass is desirable. We describe a new single-pass technique that involves further needle penetration into the posterior myometrium, under ultrasound guidance, physically displacing the obstructing membranes down the shaft away from the tip.     

Are continuity clinic patients less satisfied when residents have a heavy inpatient workload?

The purpose of this study was to assess the influence of resident non-clinic workload on the satisfaction of continuity clinic patients. Over a 2-month period in 2002, residents and patients were surveyed at the University of Kentucky internal medicine continuity clinic. Residents provided a self-report of their non-clinic workload as light or medium versus heavy or extremely heavy. Patient satisfaction was assessed with a 7-item, 10-point scale with items derived from commonly used patient satisfaction instruments. In 168 patient encounters, patients were significantly less satisfied with their clinic visit if they were seen by a resident who had a heavier workload. In addition, these patients gave significantly lower ratings with regard to the amount of time spent with the patient during the visit, and how well the resident listened and paid attention. Although alternative explanations exist, we propose that heavy hospital workload is associated with decreased patient satisfaction in resident continuity clinic.     

Budd-Chiari syndrome: computed tomographic and ultrasonographic findings

A case of Budd-Chiari syndrome is presented in which computed tomography (CT) and ultrasonography suggested the correct diagnosis and excluded adjacent tumor as the cause of hepatic vein occlusion. The CT appearance in this case (homogeneously increased attenuation of an enlarged caudate lobe) differed from the appearance previously reported (patchy liver enhancement) in Budd-Chiari syndrome. Underlying mechanisms responsible for the different CT appearance are discussed.     

Computerized tomography in the evaluation of the soft tissue component of bony lesions of the pelvis

Three cases are presented in which lesions of the bony pelvis with extraosseous soft tissue components are evaluated using computerized tomography. In each instance, computerized tomography provided precise anatomic localization of bony lesions and clearly depicted the extent of associated extraosseous masses. In all cases, the clarity of anatomic detail obtained suggests that computerized tomography represents an important new methodology for evaluation of the soft tissue component of bony lesions of the pelvis.     

A learning perspective on caring: a view from the ground up

In an interview, an adult learner with the Canadian School of Management discusses her research proposal aimed at strengthening the capability of the facility where she works to deal with clients suffering from Alzheimer's disease (AD) and other forms of dementia. The learner describes her motivation for this kind of work. She describes how she will apply some of the action learning principles recently learned to bring a mix of people together to discuss and work through issues relating to the care of clients residing in the Alzheimer unit. Canadian statistics suggest that at this time, one in three adults over the age of 85 and 1 in 13 over the age of 65 is affected with Alzheimer's or other forms of dementia. These numbers are expected to grow significantly as the population ages. The learner explains how, through her initiative, the facility will be more equipped to both meet the needs of current clients and those in the future.     

Atopic dermatitis: a new treatment paradigm using pimecrolimus

Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation. Pimecrolimus is a novel steroid-free treatment for AD. Consistently positive results have been found with pimecrolimus treatment in infants, children/adolescents, and adults. Its safety record is excellent, and studies have found no clinically relevant drug-related systemic adverse events. In this article, we first review atopic dermatitis and conventional treatment strategies. We then discuss various aspects of pimecrolimus, including pharmacologic properties, toxicology, short- and long-term studies, and safety and adverse events. Finally, we propose a new steroid-sparing treatment strategy for AD.     

Coronary artery aneurysm formation following PTCA

Since its introduction in 1977, the number of procedures and indications for PTCA have grown. With this more frequent and broader use, new complications have been reported. This report describes the formation of a new coronary artery aneurysm at the PTCA site following dilatation. The pathogenesis of aneurysmal formation following PTCA is unknown.