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Biomedical subjects

R E Morris

Publications and source records attributed to R E Morris.

At least 217 records · Page 12Linked to original sources
PubMed1988

Evaluation of the in vivo dose-response relationship of immunosuppressive drugs using a mouse heart transplant model: application to cyclosporine.

We have developed a 2-week bioassay that quantitates the effect of immunosuppressive drugs on organ allograft rejection. This assay is not only rapid and reliable, but also simple and relatively inexpensive and sparing of test substances. We refined the method by which neonatal mouse hearts are transplanted into pouches in the pinnae of ears of adult recipient mice and used cyclosporine treatment as an example of how this method might be generally applied to study the dose-response relationship of immunosuppressive drugs. Five- to 10-week-old C3H/km mice were used as cardiac recipients, and unsexed newborn BALB/c (allograft) or C3H/km (isograft) mice (24-48 hr old) were used as cardiac graft donors. The heart grafts were examined by two independent observers every other day at 10- to 20-fold magnification for up to 14 days. The immunosuppressive effect of cyclosporine was studied at doses of 3, 7.5, 15, 22.5 and 30 mg/kg per day administered i.p. The accrued data were analyzed by two methods: dose-response curves at days 12 and 14 and mean survival scores from day 8 to day 14. The dose-response curves on days 12 and 14 were similar, and the calculated ED50 values were 9.83 and 15 mg/kg/day, respectively. The results of this study demonstrate the potential usefulness and the sensitivity of the ear-heart transplantation bioassay for relative potency evaluations of immunosuppressive drugs.

Animals↗
PubMed1987

Bilateral ocular shotgun injury.

We retrospectively studied 14 patients with bilateral ocular shotgun injury in order to determine overall visual prognosis and factors affecting individual prognosis. Although only eight of 28 eyes (29%) in this series recovered visual acuity of 20/100 or better, six of 14 patients (43%) recovered at least 20/100 and eight of 14 patients (57%) recovered visual acuity of at least 20/400. Tissue destruction in the form of severe ocular disorganization or direct injury of optic nerve or macula was the primary limiting factor to visual recovery in 16 of 20 eyes (80%) not recovering to 20/100, while retinal detachment was the limiting factor in only four of these 20 eyes (20%). While extensive ocular disorganization, direct optic nerve or macular injury, no light perception on initial examination, and multiple pellet injuries were predictive of poor outcome, retinal detachment and double perforating injury were not.

Adolescent↗
PubMed1987

Recovery of vision after presumed direct optic nerve injury.

Immediate loss of light perception after direct optic nerve injury is usually irreversible. Our patient sustained presumed direct optic nerve injury because of a shotgun injury with loss of light perception, absent pupillary response, and absent visual-evoked potential. A small pupillary response was noted 12 days after injury, light perception returned by 15 days, and visual acuity was 20/100 at 4 months. A variety of pathophysiologic mechanisms may lead to visual loss after direct optic nerve injury. It is important to recognize that blindness is not always permanent in these cases despite the results of initial clinical and electrophysiologic testing.

Adolescent↗
PubMed1987

Treatment of hemorrhagic shock with intraosseous administration of crystalloid fluid in the rabbit model.

Intravenous access can be very difficult to obtain in small hypotensive infants. We studied the ability of the intraosseous route to accept a large volume of resuscitation fluid administered to hypovolemic rabbits. Hypotension induced by withdrawing one-third of the blood volume of rabbits was treated by infusion of saline, IV or intraosseously. A control group was bled, but received no saline. All three groups experienced a drop in mean arterial blood pressure (MAP) to at least 50% of the prebleed baseline value. Also, all groups' heart rates dropped to between 90 and 95% of prebleed baseline values. A ten-minute infusion of a saline volume equal to three times the volume of blood removed reversed hypotension equally by the intraosseous and IV routes. After one-half of the fluid was administered, the MAP was 107 +/- 4% and 104 +/- 11% of baseline in the intraosseous and IV groups, respectively. In contrast, the control group had a MAP of 70 +/- 8% of baseline at the same time. At the end of the fluid bolus the intraosseous group had a MAP of 97 +/- 3% of baseline and the IV group a MAP of 99 +/- 8%. The control group continued to have a low MAP of 72 +/- 6% of baseline. Heart rates rose during fluid administration in both the intraosseous and IV groups, reaching 103 +/- 2% and 99 +/- 3%, respectively, at the end of fluid administration. The control group was 88 +/- 2% of baseline at the same time. The differences between the treatment groups and the control group were significant at the .05 level. The intraosseous route will allow sufficient flow of fluid to rapidly reverse hypotension secondary to hemorrhage in a small mammal (ie, the rabbit).

Animals↗
PubMed1987

Eye Injury Registry of Alabama (preliminary report): demographics and prognosis of severe eye injury.

Each year an estimated 1.3 million Americans suffer eye injuries. There is little information in the literature regarding the prevalence, demographic characteristics, and prognosis of these patients. The Eye Injury Registry of Alabama (EIRA) serves as the first and only statewide system of its kind for the collection of information on serious eye injuries. We have analyzed 736 cases of serious eye injury (injury involving permanent structural or functional change) accumulated by the EIRA between August 1982 and May 1986. Prognosis was found to be related to early diagnosis and initial vision. Individuals with follow-up vision of 20/40 or better were found in all early diagnostic groups, and 13% of patients with no light perception on initial examination had some improvement on follow-up. The worst visual prognosis was among those patients suffering blunt eyeball rupture, of whom 40% had no light perception and 25% regained vision of 20/100 or better.

Accidents, Home↗
PubMed1987

Pharmacodynamics of cyclosporine-ketoconazole interaction in mice. Combined therapy potentiates cyclosporine immunosuppression and toxicity.

We have previously studied the pharmacokinetics of the cyclosporine-ketoconazole interaction and shown that ketoconazole inhibits the metabolism of cyclosporine in mice. In the present study we investigated the pharmacodynamics of the interaction and found that ketoconazole increased the immunosuppressive activity and toxicity of cyclosporine in vivo. Mice were treated orally with cyclosporine (25-200 mg/kg/day), ketoconazole (100 mg/kg/day), drug vehicle, or drug combination for 14 days. Immunosuppression was studied by assaying radiometrically the delayed hypersensitivity response in mice that were sensitized and challenged to keyhole limpet hemocyanin. The dose-response curve for cyclosporine was shifted to the left when cyclosporine and ketoconazole were coadministered compared with treatment with cyclosporine alone. The dose that produced 50% of the maximal immunosuppression (ED50) for cyclosporine alone was 89 mg/kg/day, whereas the ED50 for cyclosporine, when combined with ketoconazole, was 33 mg/kg/day. Ketoconazole alone was not immunosuppressive. Toxicity was measured by the length of survival during a ten-day period of treatment. Animals receiving both drugs had a significantly lower survival: the ten-day survival of animals treated with 200 mg/kg/day of cyclosporine was 100% in the absence of ketoconazole treatment and 62.5% with 100 mg/kg/day of ketoconazole. The results of our study have two important implications. First, the effect of ketoconazole on cyclosporine immunosuppression is quantitatively similar to its effect on cyclosporine kinetics. Because of this two- to three-fold increase in both unchanged cyclosporine blood levels and immunosuppression, our results suggest that unchanged cyclosporine--not its metabolites--is the primary pharmacological agent of cyclosporine in vivo immunosuppression. Second, to avoid cyclosporine-induced nephrotoxicity, it has been recommended that the dosage of cyclosporine be decreased when this drug combination is used clinically. The results of this study suggest that a decrease in cyclosporine dosage will not lower the level of immunosuppression in these patients.

Animals↗
PubMed1986

Problems in the production and use of 5 nm avidin-gold colloids.

Over the past 5 years we have encountered several problems in the production and use of 5 nm avidin-gold colloids for markers in electron microscopy. These problems include flocculation of colloids during reduction of chloroauric acid, insoluble gold pellets following ultracentrifugation, and non-specific binding of avidin-gold colloids to biological membranes. We are able to avoid these problems by: avoiding the use of crystalline chloroauric acid; succinoylating egg white avidin prior to adsorption on the gold sols; resuspending the pellets following ultracentrifugation in 5 mM phosphate buffer, pH 7.5; and using the avidin-gold colloids within 4 weeks of production.

Animals↗
PubMed1986

Reduced temperature alters Pseudomonas exotoxin A entry into the mouse LM cell.

The movement of Pseudomonas exotoxin A (PE) into the cytoplasm of mouse LM fibroblasts was followed by using inhibition of protein synthesis as a biochemical index of toxin activity; biotinyl-PE and avidin-gold colloids were used for electron microscopy. At 37 degrees C both specific antitoxin and pronase-trypsin protected cells against PE toxicity when added within seconds of warming cells, whereas methylamine was protective when added during the first 7 min of endocytosis. Lowering the temperature to 19 degrees C afforded protection when the temperature transition was accomplished within 15 min of the original endocytic event. These data suggest that PE enters an acidic compartment before reaching a step blocked by shifting cells from 37 to 19 degrees C. PE expressed toxicity for LM cells at 19 degrees C, but at a concentration 1 order of magnitude higher than that required at 37 degrees C. At 19 degrees C, antitoxin or trypsin-pronase protection was rapidly ablated. In contrast cells were fully protected by methylamine for 90 min. Using electron microscopy we demonstrated that toxin moved normally (30 s) to coated areas at 19 degrees C, but remained at this site for up to 20 min before being internalized. The majority of the toxin internalized at 19 degrees C remained in endosomes or in Golgi-associated vesicles and was not delivered to lysosomes. The results suggest that, under physiological conditions (37 degrees C), PE rapidly enters cells through coated areas, moves to an acidic compartment (i.e., the endosome), and then probably to the Golgi region en route to lysosomes. The evidence suggests that movement of toxin from endosomes or Golgi vesicles to lysosomes is blocked at 19 degrees C. We hypothesize that the active form of PE enters the cytosol, where it expresses its toxicity during fusion of Golgi-derived, toxin-laden vesicles with lysosomes.

ADP Ribose Transferases↗