Henry N. Wagner

STUDIES OF THE RETICULOENDOTHELIAL SYSTEM (RES). I. MEASUREMENT OF THE PHAGOCYTIC CAPACITY OF THE RES IN MAN AND DOG

When human serum albumin is aggregated under standardized conditions, a polymer is obtained that can be successfully used to study the phagocytic capacity of the reticuloendothelial system (RES) in man. In addition to careful control of pH, temperature, amount of agitation, and concentration of the albumin solution, it is necessary to monitor the changes in optical density, to insure adequacy of the prepared material by bioassay in man, or dog, or both, and to conduct simultameous control studies in normal subjects during the study of patients. Large doses of aggregated albumin can be safety administered over prolonged periods to human subjects without evidence of hypersensitivity or excessive radiation. The phagocytic capacity of the RES in both man and dog was determined experimentally with the analytical method of Michaelis and Menten. In man, this maximal rate of phagocytosis of aggregated albumin was 1.07 mg per minute per kg of body weight. (auth)

The role of endotoxin during typhoid fever and tularemia in man: IV. The integrity of the endotoxin tolerance mechanisms during infection

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

STUDIES OF THE RETICULOENDOTHELIAL SYSTEM (RES). II. CHANGES IN THE PHAGOCYTIC CAPACITY OF THE RES IN PATIENTS WITH CERTAIN INFECTIONS

The phagocytic capacity of the reticuloendothelial system (RES) was measured in patients with pneumococcal pneumonia typhoid fever, sandfly fever, and tularemia.

Uneven Distribution of Maternal and Fetal Placental Blood Flow, as Demonstrated Using Macroaggregates, and Its Response to Hypoxia*

A technique is described for studying the distribution of blood flow to the maternal and fetal placental vessels in sheep and dogs with radioactive labeled macroaggregates of albumin. When the maternal animal breathed room air the distribution of maternal placental blood flow was uneven among the cotyledons as well as within a given cotyledon. Fetal blood flow was also distributed nonuniformly among and within the cotyledons. The relation of maternal to fetal placental blood flow was also markedly uneven (coefficient of correlation, tau = 0.066). After the animal was made hypoxic by breathing 10-12% O(2) the distribution of maternal, fetal, and maternal/fetal placental flows became more uniform. The coefficient of correlation of maternal to fetal flow was high (tau = 0.53, P < 0.01). While the maternal animal breathed room air, after ligation of a major branch of the umbilical artery the distribution of maternal, fetal, and maternal/fetal flows in the remaining two-thirds to three-fourths of the placenta became more uniform. The correlation coefficient for maternal to fetal flow was high (tau = 0.35, P < 0.01).It appears that under normal circumstances with uneven distribution of blood flows there is a considerable portion of the placenta that does not receive blood flow in optimum quantities to promote efficient O(2) exchange. Failure to consider the influence of nonuniform maternal flow/fetal flow will result in overestimation of mean maternal-fetal oxygen tension gradients, and thus underestimation of the placental diffusing capacity for oxygen. In response to maternal hypoxia or compromise of the fetal placental circulation the distribution of maternal, fetal, and maternal/fetal flows becomes more uniform, thereby increasing the efficiency of placental O(2) exchange.

The effect of biliary obstruction on hepatosplanchnic blood flow in dogs

Abstract The response of hepatosplanchnic and other regional blood flows to CBD ligation has been studied after 1 and 2 weeks of biliary obstruction by the fractional distribution of differently labeled 25-μ carbonized microspheres injected into the left atrium. After 1 week of biliary obstruction, there was a generalized increased in effective liver blood flow and its hepatic arterial and portal venous components. The increase in the latter reflected an increase in arterial inflow to all the individual splanchnic viscera which was least in the colon. By 2 weeks, these changes had essentially returned to preoperative levels, with the exception of splenic flow. Coincident with these changes was an apparent increase in systemic arteriovenous shunting, the site of which was not determined. Possible causes underlying this early hepatosplanchnic response to biliary obstruction are discussed.

Radioactive Tracers and the Circulation

RADIOACTIVE TRACERS have been used from time to time since 1927 to study the circulation, but their broad clinical use has become routine only recently. It is likely that these techniques will be used more and more in the study of patients with circulatory and cardiac diseases. Even before the introduction of radioactive tracers, Fick, Stewart, Hamilton, Henriquez, Kety, and others developed the theoretical foundation for the use of indicators to study blood flow. Beginning in the late 1920s, Blumgart and his co-workers measured blood velocity, and Prinzmetal monitored the time course of tracers through the heart, a procedure called radiocardiography. Measurements of cardiac output, intracardiac shunts, and peripheral blood flow were among the applications of radioactive tracers that were proposed but

A quantitative method of measuring liver regeneration in the dog.

Abstract A quantitative method of measuring liver regeneration in the dog is described. Following development of this experimental method a 70% hepatectomy was performed in 36 dogs. Regeneration from 2 to 18 days was found to be extremely variable. It appeared to proceed in an exponential rather than a linear fashion.