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Campen C.J.,00 Pasteur Drive | Porter B.E.,Childrens Hospital of Philadelphia
Current Treatment Options in Neurology

Rates of regrowth after resection of subependymal giant cell astrocytoma (SEGA) are low, making surgical resection a successful and permanent therapeutic strategy. In addition to surgical resection of SEGAs, other treatment options now include medications and Gamma Knife™ therapy. Advising patients on medical versus surgical management of SEGAs is currently not easy. SEGAs have been reported to regrow if mTOR inhibitor therapy is stopped, raising the possibility that long-term medication may be required to prevent tumor growth and hydrocephalus. The question of regrowth following medication withdrawal will need to be addressed in more patients to help establish the optimal duration of therapy. The risks of surgery include acute morbidity and the permanent need for ventriculoperitoneal shunting, which must be balanced against the adverse effects of mTOR inhibitors, including immunosuppression (infections, mouth sores), hypercholesterolemia, and the need for chronic drug monitoring. Some additional benefits of mTOR inhibition in patients with tuberous sclerosis complex, however, may include shrinkage of angiofibromas and angiomyolipomas as well as a possible decrease in seizure burden. Recent reports of successful nonsurgical treatment of SEGAs are promising, and it is hoped that further specifics on dosing, duration, and long-term outcome will help patients and physicians to make informed therapeutic choices. Present treatment recommendations for SEGAs include routine surveillance neuroimaging and close clinical follow-up, paying particular attention to signs and symptoms of acute hydrocephalus. If symptoms arise, or if serial neuroimaging demonstrates tumor growth, neurosurgical intervention is recommended. When gross total resection is impossible, rapamycin and everolimus should be considered, but may not offer a durable response. © 2011 Springer Science+Business Media, LLC. Source

Price E.,00 Pasteur Drive | Artz A.S.,University of Chicago | Barnhart H.,Duke Clinical Research Institute | Sapp S.,Duke University | And 12 more authors.
Blood Cells, Molecules, and Diseases

Anemia is common in older persons and is associated with substantial morbidity and mortality. One third of anemic older adults have unexplained anemia of the elderly (UAE). We carried out a randomized, wait list control trial in outpatients with UAE and serum ferritin levels between 20 and 200. ng/mL. Intravenous iron sucrose was given as a 200-mg weekly dose for 5. weeks either immediately after enrollment (immediate intervention group) or following a 12-week wait list period (wait list control group). The primary outcome measure was changed in 6-minute walk test (6MWT) distances from baseline to 12. weeks between the two groups. Hematologic, physical, cognitive, and quality of life parameters were also assessed. The study was terminated early after 19 subjects enrolled. The distance walked in the 6MWT increased a mean 8.05 ± 55.48 m in the immediate intervention group and decreased a mean 11.45 ± 49.46 m in the wait list control group (p = 0.443). The hemoglobin increased a mean 0.39 ± 0.46 g/dL in the immediate intervention group and declined a mean 0.39 ± 0.85 g/dL in the wait list control group (p = 0.026). Thus, a subgroup of adults with UAE may respond to intravenous iron. Enrollment of subjects into this type of study remains challenging. © 2014. Source

Arai S.,00 Pasteur Drive | Miklos D.B.,00 Pasteur Drive
Expert Opinion on Biological Therapy

Importance of the field: The success of rituximab therapy in managing B cell malignancies supports its widespread application in both autologous and allogeneic hematopoietic cell transplantation. Areas covered in this review: We searched the PubMed database using the terms rituximab, stem cell transplant, autologous, or allogeneic and limited the search to clinical trials in English. In total, 92 trials were identified and 16 were reviewed in detail for significance of rituximab intervention. In this review, we will examine rituximab's emerging roles in: i) in vivo graft purging; ii) maintenance following autologous transplantation; iii) allogeneic transplant conditioning; and iv) the rationale for its use in the treatment/prevention of chronic graft-versus-host disease and post-transplant lymphoproliferative disorder. What the reader will gain: The reader will gain an understanding of the use of rituximab not only in transplants for B cell malignancies, but also its extension to other diseases where we are learning that B cells are involved in the pathogenesis. Take home message: With rituximab firmly established in the non-transplant therapy of B cell malignancies, the new challenge in transplantation is how to incorporate the drug for optimum efficacy in those patients coming to transplant with relapse after rituximab-containing therapy. © 2010 Informa UK Ltd. Source

Wong J.K.,00 Pasteur Drive | Tian Y.,00 Pasteur Drive | Shuttleworth P.,Stanford University | Caffarelli A.D.,Stanford University | And 2 more authors.
Anesthesia and Analgesia

Direct thrombin inhibitors are heparin alternatives for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We report a case of a large thrombus forming in the venous reservoir while using bivalirudin. We suggest that blood stasis associated with the full venous reservoir maintained in this case led to formation of a large thrombus at the top of the venous canister. Furthermore, activated clotting times may not accurately reflect the magnitude of anticoagulation when using direct thrombin inhibitors. (Anesth Analg 2010;111:609 -12) Copyright © 2010 International Anesthesia Research Society. Source

Bothe W.,00 Pasteur Drive | Kvitting J.P.E.,00 Pasteur Drive | Swanson J.C.,00 Pasteur Drive | Miller D.C.,00 Pasteur Drive
Journal of the Mechanical Behavior of Biomedical Materials

Progressive alterations in cardiac wall strains are a classic hallmark of chronic heart failure. Accordingly, the objectives of this study are to establish a baseline characterization of cardiac strains throughout the cardiac cycle, to quantify temporal, regional, and transmural variations of active fiber contraction, and to identify pathways of mechanical activation in the healthy beating heart. To this end, we insert two sets of twelve radiopaque beads into the heart muscle of nine sheep; one in the anterior-basal and one in the lateral-equatorial left ventricular wall. During three consecutive heartbeats, we record the bead coordinates via biplane videofluoroscopy. From the resulting four-dimensional data sets, we calculate the temporally and transmurally varying Green-Lagrange strains in the anterior and lateral wall. To quantify active contraction, we project the strains onto the local muscle fiber directions. We observe that mechanical activation is initiated at the endocardium slightly after end diastole and progresses transmurally outward, reaching the epicardium slightly before end systole. Accordingly, fibers near the outer wall are in contraction for approximately half of the cardiac cycle while fibers near the inner wall are in contraction almost throughout the entire cardiac cycle. In summary, cardiac wall strains display significant temporal, regional, and transmural variations. Quantifying wall strain profiles might be of particular clinical significance when characterizing stages of left ventricular remodeling, but also of engineering relevance when designing new biomaterials of similar structure and function. © 2011 Elsevier Ltd. Source

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