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Treatment of pernicious anemia by oral administration of vitamin B12 and glandular mucoprotein recovered from gastric juice of humans
American Federation for Clinical Research unsustained. Bone marrow eosinophils remained normal in number when there was profound peripheral eosinopenia. Striking hematocrit changes attributed to hemodilution and hemoconcentration were noted. These observations indicate that ACTH and cortisone are not primary erythropoietic “stimulants” but exert their effect indirectly by suppressing an underlying inflammatory process. TREATMENT OF PERNICIOUS ANEMIA BY ORAL ADMINISTRATION OF VITAMIN B12 AND GLANDULAR MUCOPROTEIN RECOVERED FROM GASTRIC JUICE OF HUMANS. George B. Jerq
Glass, M.D., Linn 3. Boyd, M.D. (by invitation) Michael A. Rubinstein, M.D., (by invitation) and Chester S. Svigals, M.D. (by invitation). New York Medical College, Flower & Fifth Avenue Hospitals, and Metropolitan Hospital Research Unit, .hfew York, N. Y-. The weak oral action of vitamin Bi2 (extrinsic factor) in pernicious anemia is due to its deficient intestinal absorption in this disease. This is caused by the absence of Castle’s intrinsic hematopoietic factor from the gastric juice of these patients, as shown by the effectiveness of small oral doses of vitamin Brz if administered together with a sufficient amount of normal gastric juice. The substance in the gastric juice responsible for intrinsic factor hematopoietic activity, however, has not been identified. Eight patients with proven pernicious anemia in relapse and observed for three to nine months were given daily oral doses of 7 to 30 micrograms of vitamin Bi2 to which, after a control period, a daily dose of 50 to 200 mg. of glandular mucoprotein was added. The latter was recovered from gastric contents rich in this substance. In one case in partial relapse the daily dose of 20 micrograms of vitamin Biz in association with 50 mg. of mucoprotein was insufficient to promote a hematopoietic response. In two other cases the daily administration of 7 to 10 micrograms of vitamin Bie with 50 to 100 mg. mucoprotein maintained the blood status but was insufficient for promoting a definite hematopoietic response. In the fourth case the daily administration for several weeks of 10 micrograms of vitamin Big with 200 mg. of mucoprotein caused an optimal hematopoietic response. In four other cases in complete relapse a suboptimal or optimal response was obtained after a daily dose of 50 to 150 mg. mucoprotein was added to the daily oral dose of 30 micrograms of vitamin Biz. The response was absent or very JANUARY,
1952
109
weak during the administration of the same dose of vitamin Bis alone. The data suggest that Castle’s intrinsic hematopoietic factor is contained in or is identical with the glandular mucoprotein of the human gastric juice. EFFECTS OF ACUTE HYPOXIA ON THE CIRCULATION OF THE DOG. Benjamin M.
Lewis, M.D. (by invitation) and Lewis Dexter, M.D. Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Mass. Dogs were anesthetized with morphineurethane-chloralose. Catheters were inserted into the pulmonary artery and left atria; cannulas were placed into the femoral artery and vein. Pressures were recorded with electromanometers and cardiac outputs estimated by the Fick method. Breathing mixtures containing 2.5 to 10 per cent oxygen were administered. With 10 per cent oxygen for one to five hours, arterial saturation was 50 to 75 per cent, cardiac output remained normal or increased and left atria1 and venous pressures remained unchanged. With 2.5 to 5 per cent oxygen for five to twenty minutes, arterial saturation was 4 to 25 per cent. If arterial saturation was approximately 25 per cardiac output increased without an cent, apparent increase in ventricular filling pressure (Group I). When saturation was below 25 per cent, left atria1 and sometimes systemic venous pressure rose (Group II). Cardiac output increased in a third (Group IIa). In the others, flow did not increase despite increased left ventricular diastolic filling pressure (Group IIb). Here, sharp reductions in oxygen supply and cardiac work occurred. When left atria1 pressures rose to 20 mm. Hg or more, gross pulmonary edema occurred. Pulmonary vascular resistance showed no significant change with hypoxia from the control values. The primary response to hypoxia is an attempt to maintain normal oxygen supply to the tissues by increasing cardiac output. This may or may not be accomplished by an increased ventricular diastolic filling pressure. The end result of severe anoxia is acute left and then right ventricular failure with death in acute pulmonary edema. Hypoxia apparently does not alter pulmonary vascular resistance. USE
OF PRONESTYL IN
THE
CARDIAC ARRHYTHMIAS:
TREATMENT
OF
CLINICAL AND Ex-
PERIMENTAL OBSERVATIONS: PRELIMINARY REPORT. E.
Lee Garlett, M.D., (by invitation) Keehn Berry, M.D., (by invitation) and Samuel Bellet, M.D., Philadelphia, Pa.
Glass, M.D., Linn 3. Boyd, M.D. (by invitation) Michael A. Rubinstein, M.D., (by invitation) and Chester S. Svigals, M.D. (by invitation). New York Medical College, Flower & Fifth Avenue Hospitals, and Metropolitan Hospital Research Unit, .hfew York, N. Y-. The weak oral action of vitamin Bi2 (extrinsic factor) in pernicious anemia is due to its deficient intestinal absorption in this disease. This is caused by the absence of Castle’s intrinsic hematopoietic factor from the gastric juice of these patients, as shown by the effectiveness of small oral doses of vitamin Brz if administered together with a sufficient amount of normal gastric juice. The substance in the gastric juice responsible for intrinsic factor hematopoietic activity, however, has not been identified. Eight patients with proven pernicious anemia in relapse and observed for three to nine months were given daily oral doses of 7 to 30 micrograms of vitamin Bi2 to which, after a control period, a daily dose of 50 to 200 mg. of glandular mucoprotein was added. The latter was recovered from gastric contents rich in this substance. In one case in partial relapse the daily dose of 20 micrograms of vitamin Biz in association with 50 mg. of mucoprotein was insufficient to promote a hematopoietic response. In two other cases the daily administration of 7 to 10 micrograms of vitamin Bie with 50 to 100 mg. mucoprotein maintained the blood status but was insufficient for promoting a definite hematopoietic response. In the fourth case the daily administration for several weeks of 10 micrograms of vitamin Big with 200 mg. of mucoprotein caused an optimal hematopoietic response. In four other cases in complete relapse a suboptimal or optimal response was obtained after a daily dose of 50 to 150 mg. mucoprotein was added to the daily oral dose of 30 micrograms of vitamin Biz. The response was absent or very JANUARY,
1952
109
weak during the administration of the same dose of vitamin Bis alone. The data suggest that Castle’s intrinsic hematopoietic factor is contained in or is identical with the glandular mucoprotein of the human gastric juice. EFFECTS OF ACUTE HYPOXIA ON THE CIRCULATION OF THE DOG. Benjamin M.
Lewis, M.D. (by invitation) and Lewis Dexter, M.D. Peter Bent Brigham Hospital and the Harvard Medical School, Boston, Mass. Dogs were anesthetized with morphineurethane-chloralose. Catheters were inserted into the pulmonary artery and left atria; cannulas were placed into the femoral artery and vein. Pressures were recorded with electromanometers and cardiac outputs estimated by the Fick method. Breathing mixtures containing 2.5 to 10 per cent oxygen were administered. With 10 per cent oxygen for one to five hours, arterial saturation was 50 to 75 per cent, cardiac output remained normal or increased and left atria1 and venous pressures remained unchanged. With 2.5 to 5 per cent oxygen for five to twenty minutes, arterial saturation was 4 to 25 per cent. If arterial saturation was approximately 25 per cardiac output increased without an cent, apparent increase in ventricular filling pressure (Group I). When saturation was below 25 per cent, left atria1 and sometimes systemic venous pressure rose (Group II). Cardiac output increased in a third (Group IIa). In the others, flow did not increase despite increased left ventricular diastolic filling pressure (Group IIb). Here, sharp reductions in oxygen supply and cardiac work occurred. When left atria1 pressures rose to 20 mm. Hg or more, gross pulmonary edema occurred. Pulmonary vascular resistance showed no significant change with hypoxia from the control values. The primary response to hypoxia is an attempt to maintain normal oxygen supply to the tissues by increasing cardiac output. This may or may not be accomplished by an increased ventricular diastolic filling pressure. The end result of severe anoxia is acute left and then right ventricular failure with death in acute pulmonary edema. Hypoxia apparently does not alter pulmonary vascular resistance. USE
OF PRONESTYL IN
THE
CARDIAC ARRHYTHMIAS:
TREATMENT
OF
CLINICAL AND Ex-
PERIMENTAL OBSERVATIONS: PRELIMINARY REPORT. E.
Lee Garlett, M.D., (by invitation) Keehn Berry, M.D., (by invitation) and Samuel Bellet, M.D., Philadelphia, Pa.