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F L Ramsey

Publications and source records attributed to F L Ramsey.

5 recordsLinked to original sources
PubMed1994

Effect of blood-brain barrier disruption on intact and fragmented monoclonal antibody localization in intracerebral lung carcinoma xenografts.

UNLABELLED: These studies highlight several factors that affect monoclonal antibody (Mab) localization to a tumor in the brain, including tumor permeability, nonspecific and specific binding, plasma half-life, radiolabeled antibody stability and the blood-brain barrier. METHODS: A pancarcinoma Mab [L6 IgG, F(ab')2 and Fab] and an irrelevant isotype-matched antibody [P1.17 IgG and F(ab')2] were given with and without osmotic blood-brain barrier disruption in a LX-1 human small-cell lung carcinoma intracerebral xenograft model. RESULTS: Intracerebral tumor size and permeability to antibody increased with the selection of 10, 14 or 17 days postinoculation when antibody was administered. Barrier disruption increased the delivery, particularly at earlier time points, which was dependent on antibody-specific and nonspecific binding and tumor permeability. Dehalogenation and/or antibody binding stability also appeared to affect the percent delivery. CONCLUSION: These studies demonstrate important variables that should be considered when clinical trials are designed or Mab delivery and localization in intracerebral tumor models are evaluated.

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PubMed1993

Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts.

The effect of dexamethasone on the delivery of monoclonal antibody L6 IgG to intracerebral and subcutaneous LX-1 small cell lung carcinoma xenografts was evaluated in nude rats (n = 157). Dexamethasone (0, 8, or 24 mg/m2) was given 18 hours before infusion of L6 IgG, with or without osmotic disruption of the blood-brain barrier. Compared with controls, the 8 mg/m2 dose decreased delivery of L6 IgG (12-37%) to all tissues, but the only significant decrease (P < 0.001) was in the subcutaneous tumor (37%). In the 24 mg/m2 group, L6 IgG delivery was significantly (P < 0.001) decreased to all tissues (37-60%). Dexamethasone had no effect on plasma levels. Barrier disruption significantly (P < 0.0001) increased L6 IgG delivery to intracranial tumor and surrounding brain, but not to subcutaneous tumor or plasma. The percentage of decremental effect of dexamethasone on L6 IgG delivery was the same with and without barrier disruption and was not associated with the time the animals were killed (P > 0.05). Compared with controls, the ratio of intracranial tumor to normal brain showed no change with dexamethasone, but the ratios of both intracranial and subcutaneous tumors to plasma significantly (P < 0.002) decreased with both doses. The in vitro cell binding capacity of L6 IgG to LX-1 cells remained unchanged after incubation of cells with dexamethasone over a 3-log concentration for 4 days, demonstrating no effect on antigen expression. This study suggests that dexamethasone has a clinically relevant generalized (i.e., central nervous system and systemic) vascular effect on permeability to L6 IgG monoclonal antibody.

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PubMed1992

Evaluation of a program to prevent head and spinal cord injuries: a comparison between middle school and high school.

This study was designed to test whether the Oregon THINK FIRST-Head and Spinal Cord Injury Prevention Program, developed for the high school audience and previously shown to have a beneficial effect, would have the same effect on students in middle school. During the spring of 1989, four schools (two high schools and two middle schools) participated. Two weeks before and after the presentation of the THINK FIRST program, 830 student questionnaires were distributed in classrooms. Questionnaire items were designed to measure knowledge, attitude, behavior, and demographic features. There was a significant difference between high school and middle school students on pretest knowledge (P = 0.0001). The average knowledge increase among all students was 0.81 correct responses (95% confidence interval: +/- 0.22) among 15 questions. The increment in knowledge did not differ significantly (P = 0.37) between high school and middle school students. One-way analysis of variance revealed no significant differences in pretest knowledge or knowledge increase associated with membership in Students Against Drunk Driving or acquaintance with someone having sustained a head or spinal cord injury. After the program, students were more likely to believe that there were actions they could take to keep from getting injured (P less than 0.0001). However, there was no change in self-reported seat belt use and most students reported that they "never" wore a bike helmet. The findings suggest that the THINK FIRST program is appropriate and beneficial for viewing by middle school-aged students.

Adolescent↗
PubMedDate not supplied

Effects of Gd-DTPA after osmotic BBB disruption in a rodent model: toxicity and MR findings.

OBJECTIVE: This experiment was done to evaluate the gross neurotoxicity of intravenous Gd-DTPA administered in conjunction with osmotic blood-brain barrier (BBB) disruption and to image a human small cell lung carcinoma intracerebral tumor xenograft before and after osmotic BBB disruption. MATERIALS AND METHODS: Neurotoxicity studies were performed in normal Sprague-Dawley rats following osmotic BBB disruption by the injection of 25% mannitol in the right internal carotid artery and intravenous administration of Gd-DTPA (n = 10). Animals were observed for major neurologic changes such as seizure or substantial motor defects, and after death neuropathologic examination was performed. Human small cell lung carcinoma cells were implanted intracerebrally in athymic nude rats (n = 4). Gadopentetate dimeglumine was injected intravenously and serial T1-weighted images were obtained. Blood-brain barrier disruption was produced in each animal, followed by a second dose of intravenous Gd-DTPA, and imaging studies were repeated. RESULTS: No gross neurologic toxicity was observed. Tumors showed dense enhancement in a small area, and BBB disruption resulted in marked enhancement in most of the gray matter of the right cerebral hemisphere. CONCLUSION: Gadopentetate dimeglumine appears to be safe in doses up to 21 mmol/m2 in conjunction with barrier disruption in rats. A human small cell lung carcinoma intracerebral xenograft provides a useful method to study brain tumors.

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