Treatment planning for stereotactic radiosurgery with photon beams

Stereotactic Radiosurgery (SRS) has evolved as a unique discipline that combines aspects of both surgery and radiation oncology. Technological developments in the past few decades have provided a wide array of treatment techniques, including (i) the Gamma Knife; (ii) Linac-based stereotactic techniques using circular collimators or using micro multileaf collimators (mMLCs); (iii) the Cyber Knife, using an x-band linac mounted on a robotic arm; and (iv) serial and spiral tomotherapy. This paper provides a review of the treatment planning methods for stereotactic radiosurgery. Because of the differences in planning strategies used for each SRS technique, this paper will provide both a general review of the pre-requisites and common features of SRS treatment planning and the planning techniques specific to each of the SRS techniques.     

Multicentric glioblastoma multiforme determined by positron emission tomography: a case report

The actual incidence of true multicentric glioblastoma multiforme (GBM) varies between 2.4 and 4.9% of all GBMs. True multicentric tumors are described as widespread lesions in different lobes or hemispheres, which cannot be explained by spreading along the cerebrospinal fluid or blood pathways. We present here a case of multicentric GBM identified with positron emission tomography. CASE REPORT: A 73-year-old woman with sudden onset headaches, balance problems, and one episode of syncope was diagnosed as having an irregular, contrast-enhancing, space-occupying lesion in the left-temporal-parietal region on magnetic resonance imaging (MRI). The tissue diagnosis was confirmed as GBM, and she received stereotactic radiosurgery using the Leksell Gamma Knife (Elekta Instruments, Atlanta, GA). A 3-month, follow-up, MRI scan showed a remarkable decrease in the size of the contrast-enhancing area that was targeted during radiosurgery. A suspicious area of enhancement was detected on the right side, although no surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed a large irregular neoplasm extending from the inferior left-temporal lobe into the deep parietal lobe with extremely intense FDG uptake, suggesting a very aggressive tumor. A smaller lesion was also discovered in the deep right-frontal lobe, representing a second neoplastic focus. The patient refused any further treatment. CONCLUSION: PET scans, in conjunction with MRI scans, allow for the best possible and most comprehensive diagnosis and treatment plans.     

Differential efficacy of a synthetic antagonist of VLA-4 during the course of chronic relapsing experimental autoimmune encephalomyelitis

The integrin VLA-4 has been shown to play a key role in the entry of antigen-specific T cells into the CNS during autoimmune demyelination. Treatment of animals with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, with antibodies to VLA-4 is known to suppress acute disease. In the present study, a synthetic antagonist of VLA-4 (TBC 3486) was injected subcutaneously into mice adoptively sensitized for chronic relapsing EAE. TBC 3486 was administered daily for 14 days at early (before acute signs) and late time points (during chronic disease). Early treatment led to marked delay in disease onset and reduction in clinical severity and demyelination. After termination of treatment, clinical severity remained lower than in controls for more than 1 week. TBC 3486-treated animals showing no clinical signs (at the height of disease in controls) displayed moderate levels of inflammation but little damage to myelin. Late administration of TBC 3486 to animals with chronic EAE had no effect clinically. Immunocytochemistry and Western blotting of CNS tissue from acutely treated animals supported a moderate shift toward a Th2-type cytokine profile after treatment. Thus, TBC 3486 effectively delayed and reduced the acute (but not chronic) phase of EAE, and this amelioration correlated with changes in the inflammatory molecule profile.     

Identification of 18 High Risk F8 Mutations for Inhibitor Development in 2,700 Non-Severe Hemophilia A Patients

Tijdschrift voor Kindergeneeskunde -     

A novel,noncanonical mechanism of cytoplasmic polyadenylation operates in Drosophila embryogenesis

Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation that requires two sequences in the 3′ untranslated region (UTR) of vertebrate substrates: the polyadenylation hexanucleotide, and the cytoplasmic polyadenylation element (CPE). Using a cell-free Drosophila system, we show that these signals are not relevant for Toll polyadenylation but, instead, a “polyadenylation region” (PR) is necessary. Competition experiments indicate that PR-mediated polyadenylation is required for viability and is mechanistically distinct from the CPE/hexanucleotide-mediated process. These data indicate that Toll mRNA is polyadenylated by a noncanonical mechanism, and suggest that a novel machinery functions for cytoplasmic polyadenylation during Drosophila embryogenesis.     

Introduction to Conformal Radiation Therapy-A Historical Overview

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Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.