LOCAL PROGRESSION WITH SPONTANEOUS REGRESSION OF TUBERCULOSIS IN THE BONE MARROW OF RABBITS, CORRELATED WITH A TRANSITORY ANEMIA AND LEUCOPENIA AFTER INTRAVENOUS INOCULATION.
In this series of rabbits it was found that the rabbits dying during the 1st month after an injection of I or 2 mg. of bovine tubercle bacilli show the same conditions: extreme tuberculosis of the lungs, acute splenic tumor with tuberculosis, involvement of the lymph glands, an occasional small tubercle in the liver and extensive tuberculosis of the bone marrow. The peripheral blood has shown a sharp fall in the platelet count, an anemia and a fall in the granulocytic strain of white cells, and these changes have been correlated with the condition of the bone marrow. There has also been a rise in monocytes and a fall in lymphocytes, to a reversal of the normal ratio. When the rabbits have survived the first acute phase of the disease longer than 3 to 4 weeks, there have been signs in the peripheral blood of a recovery of the bone marrow; the first indication of this has been an increase in platelets, then a rise in hemoglobin followed in 1 or 2 days by a rise in red cells and later a return of the three strains of granulocytes. The bone marrow has shown a rapid spontaneous disintegration of the epithelioid cells correlated with the appearance of increased evidence of acid-fast debris in clasmatocytes, especially clear in those that lie along the vessels. The animals that have survived into the 3rd month have all shown a hyperplastic phase of the healing marrow, both the red cells and all types of the granulocytes appearing in the peripheral blood in numbers above the normal. The epithelioid cells originally containing many bacilli all disappear from the marrow and the only sign left, possibly suggestive of the tuberculosis, is the acid-fast granules in the clasmatocytes. Finally, the marrow becomes entirely normal, giving the normal number of red cells and granulocytes to the blood. Thus, bone marrow in the rabbit has become involved in every instance with the injection of massive doses of viable bacilli. The findings at autopsy in those animals followed during the early reaction to infection confirm this directly and, since the curves of the cells in the peripheral blood of the more chronic animals were the same during the early stages of the disease as in those that died, the same conclusion seems justified from indirect inference for them. The method of healing has been a rapid disintegration of the epithelioid cells without caseation. The bone marrow heals itself entirely regardless of the progress of the disease elsewhere, so that one sees the remarkable condition of an animal recovering from the anemia and leucopenia while dying of tuberculosis elsewhere. The spleen also shows a tendency toward spontaneous healing. In the animals that have lived beyond 100 days there has been some gradual lessening of the diffuse distribution and extent of pulmonary lesions with the development of cavitation together with a marked involvement of the kidneys and lesions in the eyes.
Laboratories of The Rockefeller Institute for Medical Research.
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Sabin