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K Milam

Publications and source records attributed to K Milam.

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Hypothermia as an adjunctive treatment for severe bacterial meningitis.

Brain injury due to bacterial meningitis results in a high mortality rate and significant neurologic sequelae in survivors. The objective of this study was to determine if the application of moderate hypothermia shortly after the administration of antibiotics would attenuate the inflammatory response and increase in intracranial pressure that occurs in meningitis. For this study we used a rabbit model of severe Group B streptococcal meningitis. The first component of this study evaluated the effects of hypothermia on blood-brain barrier function and markers of inflammation in meningitic animals. The second part of the study evaluated the effects of hypothermia on intracranial pressure, cerebral perfusion pressure and brain edema. This study demonstrates that the use of hypothermia preserves CSF/serum glucose ratio, decreases CSF protein and nitric oxide and attenuates myeloperoxidase activity in brain tissue. In the second part of this study we show a decrease in intracranial pressure, an improvement in cerebral perfusion pressure and a decrease in cerebral edema in hypothermic meningitic animals. We conclude that in the treatment of severe bacterial meningitis, the application of moderate hypothermia initiated shortly after antibiotic therapy improves short-term physiologic measures associated with brain injury.

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The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA.

D-galactosamine produces an early defect in protein synthesis, independent of its effects on RNA synthesis. Here we show that the defect in protein synthesis is inherent in purified ribosomal subunits in vitro. Further, galactosamine treatment is associated with an 85% decrease in methylation of ribosomal RNA, involving all sites (2'-0-ribose and base positions), intact ribosomes from galactosamine-treated animals can be methylated to a greater extent than control ribosomes and in vitro methylation restores their functional capacity. Statistical analyses of these data, along with those with a number of other hepatotoxins, reveal a correlation coefficient of r = 0.95 (p less than 0.003) between protein synthetic capacity and ribosomal RNA methylation, and linear regression accounts for more than 90% of the observed variation. In contrast, no relationship was found between nucleolar RNA methylation and protein synthetic capacity. A relationship of borderline statistical significance was found between messenger RNA methylation and protein synthetic capacity, but it does not appear consistent with results obtained after CCl4 intoxication. These results lend strong support to the notion that methylation status of ribosomal RNA is an important control for protein synthesis in quiescent hepatocytes and that net hypomethylation is a common response to such divergent hepatotoxins as CCl4, ethionine and D-galactosamine.

Animals↗

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