The widespread acceptance of photodynamic therapy (PDT), a potential adjuvant brain tumor therapy under clinical evaluation since 1980, has been partially restrained by its potential toxicity toward normal brain tissue. This study examined PDT-produced injury of normal rat brain as a function of photosensitizer dose. Brain injury was characterized by correlating measurements of the area of cerebral edema using T2-weighted magnetic resonance images, measurement of brain water content at the lesion site, microscopic examination of histological sections through the PDT lesion, and by evaluation of the area of blood brain barrier (BBB) disruption using computerized morphometric analysis of the region of Evans blue (EB) dye-labelled albumin extravasation. Monochromatic red light (630 nm) was delivered intracerebrally using a 5-mm-long cylindrical, diffusion-tip optical fiber at a constant energy dose of 15 joules. A Photofrin dose of 2 mg/kg of body weight produced a transient breakdown in the blood brain barrier around the site of the implanted optical fiber demonstrated by magnetic resonance imaging (MRI), extravasation of EB dye and pallor on hematoxylin and eosin-stained microscopic tissue sections. A much larger area of BBB disruption was seen at a dose of 4 mg/kg of Photofrin, and this drug dose resulted in significant permanent brain injury. In this model, a Photofrin dose of 4 mg/kg body weight is not tolerated by the normal brain.
Discitis in children commonly presents with fever, back pain, irritability, and an inability to walk. An elevated ESR and characteristic changes on plain X-rays or bone scan are sufficient for diagnosis, but MRI is more sensitive and more specific, and it shows pathologic changes earlier. Intravenous antibiotics are administered when cultures of the disc space are positive, but in more than half of the cases, no organism can be grown. Symptoms are alleviated with bed-rest or external orthoses, but neither the duration nor the kind of symptomatic treatment influences outcome.
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