Performance of the pegfilgrastim on-body injector as studied with placebo buffer in healthy volunteers

Objective: The pegfilgrastim on-body injector (OBI) is a single-use, disposable, battery-powered injector that is designed to automatically deliver a single subcutaneous dose of pegfilgrastim beginning approximately 27?hours after activation and continuing over approximately 45?minutes. In this open-label study, we assessed performance of the OBI delivering placebo buffer in healthy volunteers.

Research design and methods: Healthy men and women aged 18–55 years, with a body mass index of 18–35?kg/m², were enrolled. OBIs were activated by filling them with placebo buffer, and two injectors were applied concurrently to each subject: one to the abdomen and one to the back of the upper arm. Subjects were monitored for substantial leakage during and after administration.

Main outcome measures: The primary endpoint of the study was successful delivery of placebo buffer based on a composite of the following: no substantial leakage during or after administration, green status light indicator on the injector during and after administration, and fill indicator bar at the empty position after administration. The secondary endpoint was the incidence of treatment-emergent adverse events (AEs).

Results: Of the 150 subjects enrolled, 149 (99.3%) completed the study. Study subjects were 48.0% men, and 52.0% women; 47.3% were white, 35.3% black or African American, 12.7% Asian, and 4.7% other. Mean (SD) age was 35.9 (10.8) years. Of the 297 total deliveries, 292 (98.3%) were considered successful: 147/149 (98.7%; 95% confidence interval [CI]: 95.2%–99.6%) to the abdomen and 145/148 (98.0%; 95% CI: 94.2%–99.3%) to the back of the upper arm. Five deliveries were considered unsuccessful: two due to hazard alarms, and three due to substantial leakage. The most common treatment-emergent AEs (in >2% of subjects overall) by preferred term were medical device site reaction (20.7%), catheter-site hemorrhage (8.7%), and headache (3.3%). No serious AEs were reported.

Conclusions: The pegfilgrastim OBI was well tolerated, and deliveries of placebo buffer were successful 98.3% of the time. The generalizability of these results may be limited by the conduct of this study in healthy subjects in a controlled environment.     

Platelets and antiplatelet therapy in patients with diabetes mellitus

Atherosclerotic heart disease is the leading cause of death in patients with diabetes mellitus. Platelets play a major role in the clinical manifestations of ischemic heart disease. Diabetic patients have hyperreactive platelets with exaggerated adhesion, aggregation and thrombin generation. Antiplatelet agents, including aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors, have shown significant efficacy in reducing recurrent ischemic events in patients with diabetes. Treatment with glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention reduces mortality in diabetic patients.     

Visualization of the dendritic arbor of neurons in intact 500 microm thick brain slices

Characterizing the structure and electrophysiological properties of single neurons is essential for understanding how individual cells contribute to the function of neuronal networks. Following intra-cellular recording from neurons in acute brain slices, the structure of the recorded cell has typically been examined by serial sectioning of the tissue slice and then reconstructing the neuron of interest; a labor-intensive and time-consuming process. Here, we have adapted a whole-mount immunohistochemical technique and used it to visualize the dendritic arbor of individual neurons in sections of adult CNS tissue up to 500 microm thick. Permeabilization of the slice and extensive washing allow histochemical reagents to penetrate and be washed from the section, producing limited background staining. Using this method, the cell within the slice can be sectioned optically and reconstructed using the optical sections. We present images of the dendritic trees of neurons in 500 microm thick slices of adult rat entorhinal cortex and hippocampus, labeled either immunohistochemically, or by biocytin injection following whole-cell patch clamp or sharp electrode recordings. The resolution obtained is sufficient to visualize dendritic spines deep within the section. The method is free from artifacts associated with cutting serial sections and is broadly applicable to tasks that require visualization of the fine structure of individual cells in thick slices of CNS tissue.     

Pathologic neovascularization in cartilage tumors

Tumor-induced angiogenesis is necessary to sustain radial growth of tumors. Increased microvascularity has been correlated with increased metastatic potential in breast, gastrointestinal, and gynecologic tumors, but has not been well studied in cartilaginous tumors. Grade II and Grade III chondrosarcomas have increased metastatic potential compared with Grade I tumors. One reason for this may be pathologic neovascularization. The purpose of the current study was to quantify the microvessel density of cartilage tumors. Seven Grade III, 17 Grade II, and eight Grade I chondrosarcomas, and 22 benign cartilage tumors were examined. Specimens were stained with antiCD34 antibody. Microvessel densities then were determined by direct counting and estimated using the Chalkley technique. Microvessel densities for Grade III and Grade II chondrosarcomas were 45.9 and 46.2 per high-power field and for Grade I and benign tumors the microvessel densities were 9.3 and 10.3. Microvessel densities of the aggressive tumors (Grades III and II) were greater than the microvessel densities of the nonaggressive tumors (Grade I and benign). Chalkley estimates confirmed the results. Microvascularity in cartilage tumors correlates with their biologic aggressiveness and seems promising as a variable to help with histopathologic grading and as a target for new treatment modalities.     

Successful separation of thoracopagus conjoined twins

The first successful separation of thoracopagus conjoined twins in Eastern Saudi Arabia with 2-year follow up is presented. Physical examination and radiographic studies revealed a conjunction that extended from midsternum to a common umbilicus. The shared internal organs included liver and pericardium. The separation was performed at the age of 4 months. The resulting chest wall defects in both twins were covered by dacron-reinforced silastic prosthesis. The abdominal wall defect was primarily closed in the "left twin," and covered with a dacron reinforced silastic sheet in the "right". Primary skin closure was achieved in both, following extensive mobilization of the skin. The musculoskeletal deformities in the neck, chest and vertebral column showed marked improvement 20 months after separation.     

Ollier's disease in association with adjacent fibromatosis

Ollier's disease (enchondromatosis) is a nonhereditary disorder of mesodermal dysplasia. It is characterized by the presence of multiple enchondromas that typically affect the metaphyseal ends of bones. The association of Ollier's disease with adjacent fibromatosis has, to our knowledge, not been previously described. We report a case of Ollier's disease in association with soft tissue fibromatosis adjacent to the involved upper arm.