W. Barry Wood

STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA : I. THE ACTION OF TYPE SPECIFIC ANTIBODY UPON THE PULMONARY LESION OF EXPERIMENTAL PNEUMONIA

Experimental pneumococcal pneumonia was produced in albino rats by intrabronchial inoculation of Type I pneumococci suspended in mucin. The resulting pneumonia was uniformly fatal in untreated rats. Eighty per cent of the animals so infected and treated with sulfonamide drugs 6 hours after inoculation survived the pneumonia. At the end of 1 week the surviving animals were sacrificed, and examination of the lungs showed sharply demarcated localized pulmonary lesions containing no pneumococci. Microscopic study of the lungs of treated animals sacrificed at 6, 18, 42, 66, 96, and 168 hours after the start of treatment revealed the following sequence of events. During the first 18 hours the drug apparently had little effect upon the pneumonic lesion, but at the end of 18 hours pneumococci in the edema zone began to show striking changes in their morphology, indicating bacteriostesis. Forty-two hours after the start of treatment the edema zone had disappeared, the pneumonia had ceased to spread, and the pneumococci at the margin of the lesion had been overtaken by leucocytes. Careful examination of the exudate in the periphery of the lesion revealed definite phagocytosis of pneumococci. By the 4th day no pneumococci could be found in the stained sections, and after 1 week there remained only macrophages in the rapidly clearing alveoli. In order to demonstrate the phagocytic reaction more clearly the effect of sulfonamide drugs was studied in pneumonic rats previously rendered leucopenic by exposure to x-ray. The pneumonia in these animals was relatively acellular, and the few macrophages present in each alveolus could be seen to have phagocyted large numbers of pneumococci after 18 to 42 hours of treatment. The macrophages not only phagocyted the pneumococci but ultimately destroyed them, the pneumonic lesion later going on to complete resolution. The fact that this phagocytic reaction was observed in the lungs of animals with bacteremia suggests that the phagocytosis is independent of circulating type-specific opsonins.

OBSERVATIONS UPON THE EXPERIMENTAL AND CLINICAL USE OF SULFAPYRIDINE. II. THE TREATMENT OF PNEUMOCOCCAL PNEUMONIA WITH SULFAPYRIDINE

Excerpt The rational utilization of any promising compound in the field of clinical chemotherapy is dependent upon a knowledge of its absorption by, distribution in, and excretion from the body. Ea...

The apparent activation of salmonella enteritis by oxytetracycline

Abstract A case of acute gastroenteritis due to S. muenchen is reported in which the infection appeared to have been activated by prophylactic therapy with oxytetracycline. The probable mechanism of such activation is briefly discussed.

OBSERVATIONS UPON THE EXPERIMENTAL AND CLINICAL USE OF SULFAPYRIDINE. III. THE MECHANISM OF RECOVERY FROM PNEUMOCOCCAL PNEUMONIA IN PATIENTS TREATED WITH SULFAPYRIDINE

Excerpt It has been established by a number of investigators1, 2, 3, 4, 5that sulfapyridine exercises a bacteriostatic effect upon pneumococci in vitro. Fleming1has shown that the growth of pneumoc...

THE MECHANISM OF RECOVERY IN ACUTE BACTERIAL PNEUMONIA

Excerpt Although the treatment of acute bacterial pneumonia has been revolutionized in recent years by the advent of chemotherapy, the exact mechanism of recovery is not known. Pertinent to the pro...

Action of Sulfapyridine upon Pulmonary Lesion of Experimental Pneumococcal Pneumonia

The action of type specific antiserum upon the pulmonary lesion of lobar pneumonia has been described in a previous paper. 1 Pneumonia was produced experimentally in white rats by intrabronchial inoculation of type I pneumococci suspended in mucin. The disease was uniformly fatal in untreated animals, and pneumococci were found to spread through the lung by way of edema fluid at the advancing margin of the lesion. Type specific antiserum penetrated the pneumonic lesion and apparently stopped its spread by agglutinating and immobilizing the invading organisms in the outer edema zone. The fixed pneumococci were then overtaken and were rapidly phagocytized by leucocytes. Although sulfapyridine has proven beyond any doubt to be effective in the treatment of lobar pneumonia, the mechanism by which recovery is induced is not yet understood. Fully encapsulated living pneumococci are resistant to phagocytosis unless opsonized by specific antibody, 2 , 3 and phagocytosis is the only known method by which the host can destroy these organisms. 4 Since chemotherapy often causes a crisis long before antibodies appear in the blood, 5 and sulfapyridine in the usual dosage is mainly bacteriostatic rather than bactericidal, 6 it is not at all clear how the drug brings about the final destruction of pneumococci in the lung. Thirty-eight albino rats were treated with sulfapyridine 6 hours after inoculation. The drug was suspended in 10% gum acacia and introduced into the stomach through a blunt cannula. Two hundred and fifty milligrams of sulfapyridine suspended in 4 cc of gum acacia mixture were given as an initial dose, and half of this amount in 2 cc of acacia was administered thereafter every 12 hours. In uninfected rats no toxic effects were noted after 1 week of treatment.

Factors Controlling the Release of Endogenous Pyrogen from Polymorphonuclear Leukocytes.

Excerpt The role of endogenous pyrogen in the pathogenesis of fever will have been discussed by the preceding speaker. That polymorphonuclear leukocytes constitute a major source of the endogenous ...