Ventilatory depression in naive and tolerant rats in relation to plasma morphine concentration.

1 The disappearance of morphine from specially formulated pellets containing 75 mg morphine base was measured for 10 days after they were implanted into adult rats; the morphine content decreased at a rate of 5 mg pellet daily.2 From the 2nd to the 6th day of implantation the plasma morphine concentration increased but by the 10th day had declined to only one half the concentration found on day 6.3 Six and 24 h after the pellets were removed from 6 day implanted animals the plasma concentration of morphine amounted to only one quarter to one sixth of the amount in the plasma, respectively, of animals with pellets intact.4 The pulmonary minute volume of naive and implanted rats was depressed by morphine in proportion to the plasma morphine concentration. Less depression was produced by intravenous morphine in the implanted rats than in the naive animals; the greater morphine tolerance displayed by the implanted animals could be shown by the third day of implantation and appeared to be maintained to the 10th day.5 The pulmonary minute volume of implanted rats on the 6th day was much less than the pulmonary minute volume of naive rats. Six and 24 h after the pellets were removed the pulmonary minute volume increased as the plasma morphine concentration decreased.6 The effects on the pulmonary minute volume produced by the slow release of morphine from the implanted pellets was not changed by the development of tolerance while the effects of morphine produced by rapid injection were diminished by the development of tolerance; the different effects of morphine are accordingly linked to the mode of administration.7 We conclude that the action of morphine on the pulmonary minute volume in tolerant rats following rapid injection is fundamentally different from its action following its slow release from implanted pellets, possibly due to differences in access to an undefined neuronal site.

The incidence of HLA antigens in black primary open-angle glaucoma patients.

We compared the HLA antigen frequencies in black primary open-angle glaucoma patients to those in black non-glaucomatous patients; normal, nondiseased black persons; and nondiseased North American blacks. We found no statistically significant alteration in HLA antigen frequencies in black open-angle glaucoma patients as compared to a control population.

Primary open-angle glaucoma and sensitivity to corticosteroids in vitro.

Corticosteroid inhibition of mitogen induced lymphocyte transformation was studied in patients with definite or suspected primary open-angle plaucoma (POAG). Patients without glaucoma served as normal controls. From a dose response curve with prednisolone-21-PO4 or prednisolone the value of 50% inhibition (I50) was determined for each patient. In Series I it was necessary to disqualify 70% of the data whereas in Series II less than 5% were excluded. In Series I the median I50 (M X 10(-8) prednisolone-21-PO4) was 12 for 11 controls and 8 for 18 total POAG'S (p less than .01). In Series II the opposite result was obtained. The median I50 was 8 for 49 controls and 12 for 79 total POAG'S (p less than .01). In series II similar results were obtained with prednisolone. There was no difference between definite and suspected glaucoma patients. The cause of the discrepancy between the present two series and among the other published studies is not clear. The source of normal controls, from either an eye clinic or volunteer groups, may be a factor.