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Effect of cortisone acetate on acute exudative streptococcal tonsillitis and pharyngitis: Clinical and immunologic aspects
American Federation for Clinical Research of the spleen which can be obtained by splenic puncture. The architecture of the spleen is maintained and foci of immature granulocytes, normohlasts and megakaryocytes are observed. Several reports indicate that chronic benzene poisoning may cause this condition. No exposure to hcnzene was present in the patients observed in this series. It is generally agreed that recognition of this condition is important because splenectomy and x-ray therapy are usually harmful. Trre HARGRAVES “1,. E.” CELL: OBSERVATION ok ITS FORMATION.John B. Moyer, M.D. and
George S. Fisher, M.D.,
Duluth, Minn.
I_. E. cells may he found in marrow buffy coat concentrate preparations from cases of disseminated lupus erythematosus as well as in the blood buffy coat. They can be induced in human or animal marrow preparations, and under certain circumstances in peripheral blood, by mixture with the “L. E. factor.” Three elements are necessary for L. E. cell formation: (1) active phagocytes to ingest (2) nucleoprotein in the presence of (3) the L. E. factor. The L. E. cell inclusion appears to be derived from nucleoprotein. It appears that any effective source of nucleoprotein must contain lymphocytic nuclei. A relatively pure suspension of lymphocytes was obtained from a case of chronic lymphocytic leukemia. After alteration !I). freezing to remove the cytoplasm, the nuclei were ingested in abundance by neutrophils in the presence
of the L. E. factor.
tion by freezing of neutrophils
of relatively Supravital
made of a mixture
containing
bare lymphocytic
factor. i\ctive by neutrophils
altera-
failed to provide a suitable source
of nucleoprotein. altered,
Similar
pure suspensions observations
were
fresh neutrophils,
nuclei and the L. E.
phagocytosis of the bare nuclei and formation of typical L. E.
cells was witnessed. This evidence lends support to the proposition that the L. E. cell is the result of ingestion of a lymphocyte nucleus by a phagocyte. LIVER FUNCTION DURING CORTISONETHERAPY. .V. C. Percefull, M.D. and ,7. H. Holmes, M.D.,
I)cnver, Cvl0. Stud& of liver function were carried out in fifteen patients before, during and after cortisone therapy. The following determinations were included in these studies: thymol turbidity, serum bilirubin, bromsulfalein, van den Bergh, APRIL,
1951
513
icteric index, prothrombin time, total cholesterol, cholesterol-ester ratio and serum esterase. Our results indicate that cortisone therapy, even for periods up to three months or in amounts up to 10 gm., produces no startling abnormality in any of these liver function tests. This was true even in two patients with liver disease. In several instances there was a slight elevation in the values for thymol turbidity during cortisone therapy which returned 10 normal after the drug was stopped. In two instances in which there was an elevation of thymol turbidity prior to therapy the values decreased in association with cortisom administration. A significant elevation in the serum cholesterol was found in three instances and minor elevations in five. The serum esterase values decreased slightly in the majority of cases. EFFECT OF CORTISONE ACETATE ON ACUTE EXUDATIVE STREPTOCOCCALTONSILLITISAND PHARYNGITIS: CLINICAL AND IMMUNOLOGIC
Edward 0. Hahn, Cap. M.C., AlTS (by invitation), Charles H. Rammelkamp, Jr., M.D., Harold B. Houser, Capt. M.C., ACTS (by invitation), Lewis W. Wannamaker, Capt. M.C., ALJS and Floyd W. Denny, Cult. M.C., A US, Cheyenne, Wyo. ASPECTS.
The pituitary and adrenal hormones play an important role in the reactions of the body to stress. One of the common stress reactions in man is infection. Since there is little information concerning the effect of these hormones in infections, the adrenal hormone, cortisone, was administered tococcal
to eighty--seven patients with strep-
exudative
tonsillitis;
another
eighty-
seven served as controls. A total of 500 or 600 was administered over five mg. of cortisone days.
Observations
included
acute illness, the suppurative
the effect
on the
and late non-sup-
purative complications and antibody formation. Therapy resulted in no alteration of the symptoms or physical signs. However, the treated group exhibited prolonged fever. Three suppurative complications developed in the controls. During cortisone treatment one patient developed
gangrenous
appendicitis
with signs of
peritonitis. Rheunlatic fever dc:\~cloped in two treated and five conrrol p&rnts. .\n additional six treated and two control patients showed prolonged P-R intervals three weeks after the illness. In those who received cortisone the antistreptolysin titers were slightly lower than in the
520
American Federation for Clinical Research
controls at six days but higher at two, three and four weeks. EFFECTSOF CORTISONEIN GLOMERULONEPHRITIS AND THE NEPHROPATHY OF DISSEMINATED LUPUS ERYTHEMATOSUS.B. I. Heller, M.D.,
W. E. Jacobson, M.D. and J. F. Hammarsten, M.D. (by invitation), Minneafiolis, Minn. Cortisone was administered to four patients in various phases of glomerulonephritis and to two patients with disseminated lupus erythematosus with renal involvement. The patients were placed on a constant diet, and control observations of the blood pressure, renal plasma flow, glomerular filtration rate and electrolyte balance were made. Moderate hypertension developed in one patient with the nephrotic phase of chronic glomerulonephritis, and severe hypertension ensued in both patients with lupus erythematosus. Transient alterations in renal function, manifested by increases in renal plasma flow, or glomerular filtration rates, or both, were observed. However, the basic pathologic process in the glomerular capillaries was unaltered as indicated by persistence of hematuria and albuminuria in all cases. In some instances albuminuria actually increased. The effects of costisone upon electrolyte balance were similar to those previously reported in the literature except for observations in one patient with disseminated lupus erythematosus. The administration of cortisone in this patient was associated with a significant rise in serum potassium and fall in serum sodium concentration. This phenomenon was again observed when cortisone therapy was re-instituted. It is concluded that cortisone does not favorably alter the course of glomerulonephritis and the nephropathy of disseminated lupus erythematosus. EFFECTOFADRENAL CORTICALEXTRACT,ACTH, CORTISONE AND H. P. C. (3-HYDROXY-2 PHENYLCINCHONINICACID) ON JOINT PERMEABILITY. J. Hidalgo, B.S., C. D. McClure, B.S.,
J. B. Henderson, B.S., R. W. Whitehead, M.D. (all by invitation); (introduced by) Char&y J. Smyth, M.D., Denver, Colo. In an attempt to evaluate the action on membrane permeability of an adrenal cortical extract (ACE) prepared in this laboratory, we tried to measure the rate of excretion of phenolsulfonphthalein (P. S. P.) injected into the synovial capsule of the rabbit. The method of Seifter was used except that the knee joint was entered.
Eleven rabbits were standardized by injecting P. S. P. and urine samples were collected at ten-minute intervals for a period of 135 minutes. The same rabbits after three weeks rest were injected with the drug under study before the P. S. P. was given. Nembutal was used as an anesthetic and supplemented by ether when necessary. The ACE prepared by us, as well as a similar extract supplied by Wilson Laboratories, proved to have no effect on the time of appearance of the dye in the urine or on the rate of its excretion. Cortisone (Merck) and hydroxy-phenylcinchoninic acid (H. P. C.) were also found to be devoid of effect on membrane permeability to the dye. Within the limits of experimental error both the control curves and those obtained following the drugs could be superimposed. METABOLIC EFFECTS OF ACTH UPON PREEXISTINGDIABETESMELLITUS. Stefan S. Fajans,
M.D. and Jerome W. Corm, M.D. (by invitation); (introduced by) William D. Robinson, M.D., Ann Arbor, Mich. Administration of ACTH produces a diabetic state and insulin resistance in some normal individuals. Both ACTH and Cortisone have been observed to intensify hyperglycemia and glycosuria when given to diabetics. Ketonemia and ketonuria have been found to increase sharply when cortisone is administered to patients having both diabetes mellitus and Addison’s disease. Careful study of the metabolic effects of ACTH
upon
pre-existing
seemed important
diabetes
but justification
mellitus
was lacking.
To satisfy the latter requirement extensive metabolic balance studies were performed upon a severely diabetic
patient
who received
a large
amount of ACTH over a twenty-two-day period for the purpose of influencing a recently developed leukemia. The more significant follows:
(1) Great
observations
intensification
were
as
of the diabetic
state; on the last ACTH day glycosuria exceeded carbohydrate intake by 100 gm.; (2) tremendous negative nitrogen balance; on the last ACTH day nitrogen excretion exceeded nitrogen intake by 23 gm.; (3) insulin resistance; (4) surprising absence of significant ketonemia and ketonuria; (5) increased activity of the leukemia; (6) hypertrophy of the adrenal cortices at autopsy. ACTH appears either to decrease ketogenesis or to increase ketolysis. AMERICAN
JOURNAL
OF
MEDICINE
George S. Fisher, M.D.,
Duluth, Minn.
I_. E. cells may he found in marrow buffy coat concentrate preparations from cases of disseminated lupus erythematosus as well as in the blood buffy coat. They can be induced in human or animal marrow preparations, and under certain circumstances in peripheral blood, by mixture with the “L. E. factor.” Three elements are necessary for L. E. cell formation: (1) active phagocytes to ingest (2) nucleoprotein in the presence of (3) the L. E. factor. The L. E. cell inclusion appears to be derived from nucleoprotein. It appears that any effective source of nucleoprotein must contain lymphocytic nuclei. A relatively pure suspension of lymphocytes was obtained from a case of chronic lymphocytic leukemia. After alteration !I). freezing to remove the cytoplasm, the nuclei were ingested in abundance by neutrophils in the presence
of the L. E. factor.
tion by freezing of neutrophils
of relatively Supravital
made of a mixture
containing
bare lymphocytic
factor. i\ctive by neutrophils
altera-
failed to provide a suitable source
of nucleoprotein. altered,
Similar
pure suspensions observations
were
fresh neutrophils,
nuclei and the L. E.
phagocytosis of the bare nuclei and formation of typical L. E.
cells was witnessed. This evidence lends support to the proposition that the L. E. cell is the result of ingestion of a lymphocyte nucleus by a phagocyte. LIVER FUNCTION DURING CORTISONETHERAPY. .V. C. Percefull, M.D. and ,7. H. Holmes, M.D.,
I)cnver, Cvl0. Stud& of liver function were carried out in fifteen patients before, during and after cortisone therapy. The following determinations were included in these studies: thymol turbidity, serum bilirubin, bromsulfalein, van den Bergh, APRIL,
1951
513
icteric index, prothrombin time, total cholesterol, cholesterol-ester ratio and serum esterase. Our results indicate that cortisone therapy, even for periods up to three months or in amounts up to 10 gm., produces no startling abnormality in any of these liver function tests. This was true even in two patients with liver disease. In several instances there was a slight elevation in the values for thymol turbidity during cortisone therapy which returned 10 normal after the drug was stopped. In two instances in which there was an elevation of thymol turbidity prior to therapy the values decreased in association with cortisom administration. A significant elevation in the serum cholesterol was found in three instances and minor elevations in five. The serum esterase values decreased slightly in the majority of cases. EFFECT OF CORTISONE ACETATE ON ACUTE EXUDATIVE STREPTOCOCCALTONSILLITISAND PHARYNGITIS: CLINICAL AND IMMUNOLOGIC
Edward 0. Hahn, Cap. M.C., AlTS (by invitation), Charles H. Rammelkamp, Jr., M.D., Harold B. Houser, Capt. M.C., ACTS (by invitation), Lewis W. Wannamaker, Capt. M.C., ALJS and Floyd W. Denny, Cult. M.C., A US, Cheyenne, Wyo. ASPECTS.
The pituitary and adrenal hormones play an important role in the reactions of the body to stress. One of the common stress reactions in man is infection. Since there is little information concerning the effect of these hormones in infections, the adrenal hormone, cortisone, was administered tococcal
to eighty--seven patients with strep-
exudative
tonsillitis;
another
eighty-
seven served as controls. A total of 500 or 600 was administered over five mg. of cortisone days.
Observations
included
acute illness, the suppurative
the effect
on the
and late non-sup-
purative complications and antibody formation. Therapy resulted in no alteration of the symptoms or physical signs. However, the treated group exhibited prolonged fever. Three suppurative complications developed in the controls. During cortisone treatment one patient developed
gangrenous
appendicitis
with signs of
peritonitis. Rheunlatic fever dc:\~cloped in two treated and five conrrol p&rnts. .\n additional six treated and two control patients showed prolonged P-R intervals three weeks after the illness. In those who received cortisone the antistreptolysin titers were slightly lower than in the
520
American Federation for Clinical Research
controls at six days but higher at two, three and four weeks. EFFECTSOF CORTISONEIN GLOMERULONEPHRITIS AND THE NEPHROPATHY OF DISSEMINATED LUPUS ERYTHEMATOSUS.B. I. Heller, M.D.,
W. E. Jacobson, M.D. and J. F. Hammarsten, M.D. (by invitation), Minneafiolis, Minn. Cortisone was administered to four patients in various phases of glomerulonephritis and to two patients with disseminated lupus erythematosus with renal involvement. The patients were placed on a constant diet, and control observations of the blood pressure, renal plasma flow, glomerular filtration rate and electrolyte balance were made. Moderate hypertension developed in one patient with the nephrotic phase of chronic glomerulonephritis, and severe hypertension ensued in both patients with lupus erythematosus. Transient alterations in renal function, manifested by increases in renal plasma flow, or glomerular filtration rates, or both, were observed. However, the basic pathologic process in the glomerular capillaries was unaltered as indicated by persistence of hematuria and albuminuria in all cases. In some instances albuminuria actually increased. The effects of costisone upon electrolyte balance were similar to those previously reported in the literature except for observations in one patient with disseminated lupus erythematosus. The administration of cortisone in this patient was associated with a significant rise in serum potassium and fall in serum sodium concentration. This phenomenon was again observed when cortisone therapy was re-instituted. It is concluded that cortisone does not favorably alter the course of glomerulonephritis and the nephropathy of disseminated lupus erythematosus. EFFECTOFADRENAL CORTICALEXTRACT,ACTH, CORTISONE AND H. P. C. (3-HYDROXY-2 PHENYLCINCHONINICACID) ON JOINT PERMEABILITY. J. Hidalgo, B.S., C. D. McClure, B.S.,
J. B. Henderson, B.S., R. W. Whitehead, M.D. (all by invitation); (introduced by) Char&y J. Smyth, M.D., Denver, Colo. In an attempt to evaluate the action on membrane permeability of an adrenal cortical extract (ACE) prepared in this laboratory, we tried to measure the rate of excretion of phenolsulfonphthalein (P. S. P.) injected into the synovial capsule of the rabbit. The method of Seifter was used except that the knee joint was entered.
Eleven rabbits were standardized by injecting P. S. P. and urine samples were collected at ten-minute intervals for a period of 135 minutes. The same rabbits after three weeks rest were injected with the drug under study before the P. S. P. was given. Nembutal was used as an anesthetic and supplemented by ether when necessary. The ACE prepared by us, as well as a similar extract supplied by Wilson Laboratories, proved to have no effect on the time of appearance of the dye in the urine or on the rate of its excretion. Cortisone (Merck) and hydroxy-phenylcinchoninic acid (H. P. C.) were also found to be devoid of effect on membrane permeability to the dye. Within the limits of experimental error both the control curves and those obtained following the drugs could be superimposed. METABOLIC EFFECTS OF ACTH UPON PREEXISTINGDIABETESMELLITUS. Stefan S. Fajans,
M.D. and Jerome W. Corm, M.D. (by invitation); (introduced by) William D. Robinson, M.D., Ann Arbor, Mich. Administration of ACTH produces a diabetic state and insulin resistance in some normal individuals. Both ACTH and Cortisone have been observed to intensify hyperglycemia and glycosuria when given to diabetics. Ketonemia and ketonuria have been found to increase sharply when cortisone is administered to patients having both diabetes mellitus and Addison’s disease. Careful study of the metabolic effects of ACTH
upon
pre-existing
seemed important
diabetes
but justification
mellitus
was lacking.
To satisfy the latter requirement extensive metabolic balance studies were performed upon a severely diabetic
patient
who received
a large
amount of ACTH over a twenty-two-day period for the purpose of influencing a recently developed leukemia. The more significant follows:
(1) Great
observations
intensification
were
as
of the diabetic
state; on the last ACTH day glycosuria exceeded carbohydrate intake by 100 gm.; (2) tremendous negative nitrogen balance; on the last ACTH day nitrogen excretion exceeded nitrogen intake by 23 gm.; (3) insulin resistance; (4) surprising absence of significant ketonemia and ketonuria; (5) increased activity of the leukemia; (6) hypertrophy of the adrenal cortices at autopsy. ACTH appears either to decrease ketogenesis or to increase ketolysis. AMERICAN
JOURNAL
OF
MEDICINE