George M. Hass

Vital staining, serum albumin and the blood-brain barrier.

Vital staining was studied by quantitating the amounts of Evans blue and serum albumin in muscle and in abnormal brain. On the basis of differences in the ratio of dye to albumin in tissue and in serum, it was concluded that the coloration of tissue involves both the presence of serum albumin in tissue and the binding of dye not associated with serum albumin by tissue. The mode of binding of free dye by edematous cerebral tissue was studied by comparing the chemical structures of a series of acid dyes which did and did not function as vital stains. It was concluded that substantivity for edematous cerebral tissue requires the presence on the dye molecule of paired widely separated electron-donating hydrogen bond forming groups placed away from the solubilizing acid groups. It is suggested that the primary mode of binding for Evans blue in tissue is through the formation of hydrogen bonds between the azo groups of the dye and the hydroxy groups of tissue polysaccharides. These findings are conceptually related to the blood-brain barrier in that the presence of staining in the brain reflects the presence of increased amounts of albumin either at the time of observation or at some time in the past.

The Chemistry of Isolated Edema Fluid in Experimental Cerebral Injury

Focal areas of hemorrhagic necrosis were produced in the brains of anesthetized dogs by a freezing technique which has been described in previous publications (Clasen, et al., 1953). Briefly, this consisted of the application of a freezing instrument cooled by liquid nitrogen to the exposed intact skull. The instrument was left in place for five–ten minutes. This resulted in a circumscribed lesion involving both gray and white matter in the underlying brain. In the first hour after injury, cellular damage was restricted to the lesion. Four hours after injury, histologic evidence of edema was seen both in the lesion and in the adjacent white matter. Both areas showed positive staining by the periodic acid-Schiff (PAS) technique (Clasen, et al., 1957).

Interrupted hypothermia in experimental cerebral edema

IN A PREVIOUS REPORT it was shown that cerebral edema induced by focal freezing of the brain in monkeys could be effectively treated by sustained systemic hyp0thermia.l This report deals with interrupted hypothermia. Although the present quantitative figures are less decisive than those in the previous report, we have interpreted them as indicating a suppression of both hemorrhage and edema in the damaged hemisphere.

Reserpine in experimental cerebral edema.

THE EXPERIMENTS to be reported represent a continuation of work done on cerebral injury in monkeys. Standard injuries were produced by freezing through the intact skull. This resulted in an area of hemorrhagic necrosis accompanied within four hours by the development of edema in and around the lesion. Efforts were then made through chemical analyses of the damaged tissue to evaluate various forms of therapy designed to alleviate this edema. Previous reports have dealt with intravenous hypertonic urea given six hours after injury1 and steroids given twelve hours after injury.2 The present report deals with reserpine. The rationale for the use of this drug was the report by Bulle3 that cerebral edema, as judged by vital staining, could be induced in mice by the intracerebral injection of serotonin and that this reaction could be suppressed by pretreatment with reserpine. In addition, Levine and associates4 have shown that this type of edema shows a positive reaction with the periodic acid-Schiff (PAS) technique. The edema associated with freezing lesions is strongly PAS positive. In testing the reserpine, the time of sacrifice was increased from twelve to twentyfour hours in order to allow a greater time for possible drug action.

Protective Effect of Magnesium Deficiency on Experimental Allergic Encephalomyelitis in the Rat.

Summary Acutely magnesium deficient rats exhibit hyperemia of the skin, leukocy-tosis, eosinophilia, degranulation of mast cells and histaminuria. These changes are preventable with antihistaminic therapy. The histological lesions of more prolonged magnesium deficiency bear a resemblance to those of delayed hypersensitivity. Because of the suggestion of a hyperimmune state in magnesium deficiency, an attempt to produce experimental allergic encephalomyelitis (EAE) in magnesium deficient rats was made. The results show that, rather than enhancing the development of EAE, magnesium deficiency exerts a protective effect. Histological evidence of EAE occurred in 70% of control rats fed normal diets and in only 18% of rats started on a magnesium deficient diet at various intervals before and after injection of the encephalitogenic mixture. Furthermore, the degree of EAE in magnesium deficient rats was inversely proportional to the severity of the myopathy characteristic of magnesium deficiency. The reason for the resistance of the magnesium deficient animal to EAE remains obscure.

Uteroplacental trauma as a method of conditioning the maternal host to adult homografts.

Treatment of the pregnant or nonpregnant rabbit with the leukocytes of a graft donor prior to grafting with musculofascial tissues always resulted in a reproducible modification of the classical homologous tissue reaction.l*z This consisted of a fibrocollagenous encapsulation of the homograft with varying degrees of vascular penetration by the host in the absence of inflammation. In spite of the frequently rich vascularization, fibroblastic proliferation and collagen deposition were curiously impaired as well as autolysis and absorption of skeletal muscle fibers within the musculofascial zone of the homograft. The aforementioned modification was also observed with great frequency in nonpregnant hosts pretreated with pooled embryonic tissues (7 to 11 per litter) or pooled placental tissues (7 to 11) prior to grafting with musculofascial tissues from adult random donor^.^.^ In view of the conditioning mechanisms inherent in embryonic tissues as well as placental tissues following transplantation and the fact that cells from the uteroplacental sites are known to enter the circulation of the pregnant rabbit following trauma,6 the following experiments were designed to characterize the maternal host homograft interaction in pregnant rabbits receiving uteroplacental trauma prior to grafting.

Chronic Pulmonary Emphysema and Cor Pulmonale A Clinical-Pathologic Conference

DR. C. BRUCE TAYLOR: The case for discussion is not being presented as an unusual case but instead as an example of a common but poorly understood disease process for which there is no very effective treatment. After presentation of the clinical abstract, Dr. Paul will discuss the clinical findings and differential diagnosis. Following this I shall briefly outline the postmortem findings and then we shall discuss certain problems illustrated by this case.