In the light of advances in computerized tomography (CT), we have retrospectively evaluated the assumptions that underlie the radiation therapy of glioblastoma: (1) No neuroradiologic technique provides an accurate delineation of tumor bulk and location, (2) glioblastoma is commonly multicentric, and (3) a major source of therapeutic failure is recurrence beyond radiotherapy fields. 1. CT scans, performed on glioblastoma patients within 2 months of postmortem examination, defined both gross and microscopic tumor extent (within a 2-cm margin) in all but 6 of 35 patients evaluated. The major source of error was subependymal spread (four patients). 2. Multicentricity occurred in only 4% of untreated and 6% of treated (radiotherapy with or without chemotherapy) patients. All multicentric lesions were identified on CT scans. 3. Serial CT scans on 42 patients revealed that glioblastoma recurred within a 2-cm margin of the primary site in 90%. Occurrences outside this margin were accurately delineated by CT in all instances. Because most patients show recurrence within or in close proximity to the original site, current radiation doses would appear to be inadequate for therapy of the primary tumor. CT scan accuracy may permit smaller-field and higher-dose irradiation therapy for glioblastoma.
This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.
The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of
continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis
(RRMS). The objective of this study was to evaluate up to 15 years of GA as a
sole disease-modifying therapy. Two hundred and thirty-two patients received at
least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%,
Ongoing cohort) continued as of February 2008. Patients were evaluated every 6
months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were
8.6 ±5.2, 4.81 ±3.69, and 13.6 ± 1.3 years and
mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing
cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs)
maintained a decline from 1.12±0.82 at baseline to 0.25 ±
0.34 per year; 57% had stable/improved EDSS scores (change ± 0.5
points); 65% had not transitioned to secondary progressive multiple sclerosis
(SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA
therapy (the mITT cohort), ARRs declined from 1.18 ± 0.82 to 0.43
± 0.58 per year; 54% had stable/improved EDSS scores; 75% had not
transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion,
multiple sclerosis patients with mean disease duration of 22 years administering
GA for up to 15 years had reduced relapse rates, and decreased disability
progression and transition to SPMS. There were no long-term safety issues.
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