Acute ultrastructural response of hypoxic hypoxia with relative ischemia in the isolated brain.

The acute cortical response to surgical brain isolation and subsequent extracorporal normoxic or 30 min hypoxic (PaO2 = 20 mm Hg) perfusions (hypoxic hypoxia with relative ischemia) was evaluated. Cerebral blood flow, arterial pH and CO2 were maintained constant during both perfusions; only the arterial oxygen content was changed. The isolated brain model used in this and previous investigations produces no qualitative ultrastructural changes in the neocortex following brain isolation and normoxic perfusion. However, the acute cortical structural response to 30 min of hypoxic hypoxia with relative ischemia demonstrated a number of important observations. Hypoxic hypoxia produced ultrastructural responses common to cerebral ischemia such as nuclear chromatin clumping, nucleolar condensation and cytoskeletal breakdown. Although neuronal abnormalities seen after 30 min of hypoxic hypoxia were similar to those acute neuronal changes observed following complete cerebral ischemia without recirculation, they differed three ways: (a) mitochondrial swelling and microvacuolation were observed in many cortical pyramidal neurons. (b) Glycogen particles within astroglial processes were observed even after a 30-min period of hypoxic hypoxia. (c) Perivascular astroglial swelling was minimal despite considerable perineuronal swelling. In contrast, incomplete cerebral ischemia produces mitochondrial changes similar to those in hypoxic hypoxia but also causes the depletion of tissue glycogen and perivascular glial swelling. Thus, hypoxic hypoxia with relative ischemia produces a unique acute ultrastructural response compared to either complete or incomplete cerebral ischemia.

"How to avoid dying from cancer ... now and later"--a course to reach the lay public.

The context, history, course description, measures and foundations for success, and future enhancements are described for the Health Education course, "How to Avoid Dying from Cancer ... Now and Later." Since 1981 this course has been offered once annually at The Ohio State University for academic credit and has averaged an enrollment of 354 undergraduate, graduate, and continuing education students. Over the years this course, originated by a surgical oncologist, has earned its own title and entry in the academic course offerings and has demonstrated success both quantitatively and qualitatively. Quantitative indicators of success include enrollment trends, diversities of students enrolled, student evaluations of the course, and data on the instructional effectiveness of this course. Qualitative indicators of success include favorable publicity through the local media, top ratings for summer radio programs based on this course, and the National University Continuing Education Faculty Service Award given to one of the authors in 1985. Four factors account for much of the success of this course.

Effect of blood pH and ischemia on kinetic constants for cerebral glucose transport.

In 117 experiments, the isolated canine brain was subjected either to 4-min pulses with blood ranging from pH 6.8 to 7.8, 30 min of hypoxia (PaO2 30 mmHg or 40 mmHg), or 30 min of complete ischemia followed by 60 min of perfusion with normal oxygenated blood. Unidirectional and net glucose fluxes were measured under all experimental conditions, and kinetic constants were calculated for unidirectional transport at each pH and after ischemia. In brains perfused with blood having a PaO2 of 30 or 40 mmHg, we observed a 58 and a 55% increase, respectively, in the net flux; however, there was no significant change in the unidirectional flux either during hypoxia or during the recovery period. Exposure of the brains to blood with a pH of 6.8, 7.0, and 7.2 had no effect on the unidirectional flux; however, as pH was raised above 7.4 both the Km and Vmax increased, reaching a maximum of 12.06 +/- 2.34 mM and 2.38 +/- 0.28 mumol X g-1 X min-1, respectively, at pH 7.8. The V/K ratio was unchanged. After 30 min of ischemia, there was a significant change (P less than 0.05) in the Km of the unidirectional glucose transport process from a control value of 5.84 +/- 1.75 mM to 17.40 +/- 5.50. These studies suggest that unidirectional flux is impaired after ischemia due to a decrease in the carrier's affinity for glucose; however, the observed changes are apparently unrelated to a fall in tissue pH. A similar mechanism is believed to be responsible for the decrease in unidirectional glucose flux after hypoxia.