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Use of aureomycin in the treatment of congenital fibrocystic disease
Western Society for Clinical Research published data could be found on quantitative urinary output of ingested uranic acids. Eight tests were conducted in two fasting normal males. Each person ingested 2 to 6 gm. of galacturonic acid or glucuronolactone after collecting a one-hour urine specimen. Urines were collected hourly for the next five to six hours. Uranic acids were estimated by the method of Hanson, Mills and Williams. Equivalent weights of galacturonic acid and glucuronolactone gave identical calibration curves. In fasting control tests one individual excreted an average of 11.3 (10.1 to 12.1) mg. and the other 12.5 (12.2 to 12.8) mg. glucuronic acid per hour. Urine uranic acid increased about 60 to 65 per cent over the initial output in one to three hours after intake of galacturonic acid. Increased excretion persisted for five to six hours. Only 1 per cent of the administered galacturonic acid appeared during this time. On the other hand glucuronolactone produced a seven- to ninefold increase over the initial output in the first hour. This declined to the original value in approximately seven hours. During this time 10 to 15 per cent of the ingested glucuronolactone was recovered in the urine. Apparently the body may utilize 85 per cent or more of the uranic acids studied assuming, of course, complete intestinal absorption. EFFECT OF HISTAMINE UPON THE LEUKOCYTE LUNG REMOVAL MECHANISM IN MAN. Howard R. Bierman, * Keith H. Kelly, Edward J, Smith and Nicholas L. Petrakis. Division of Medicine, University of California School of Medicine, San Francisco, Calif. The immediate leukopenia following intravenous histamine administration is well known. This leukopenia has been thought to be due to pooling of leukocytes in the spleen, liver and splanchnic capillaries associated with the hypotension. By sampling blood from the right and left ventricle or large artery, it was possible to determine the number of leukocytes entering and leaving the pulmonary circulation during and after the intravenous administration of 0.1 to 0.3 mg. of histamine phosphate (as base). The findings indicate that the leukopenia is due to the cells being removed from the circulation by the lungs. Furthermore the decrease occurs exclusively in the myeloid series, the agranulocytes exhibiting no significant alteration. The leukopenia is transient and the lungs then discharge the myeloid cells into the circulation. This ebb
and flow tide of white blood cells into and out of the circulation can occur rapidly and is influenced by respirations. These findings support the original contention that the pulmonary circulation contains a potent mechanism for controlling the leukocyte level in the peripheral blood in man. Further implications will be discussed. DISTRIBUTIONOF DICITOXIN IN THE ANIMAL BODY AFTER ITS PARENTERALADMINISTRATION.Reni Bine, Jr., Meyer Friedman, * and Sanford 0. Byers. Mount Zion Hospital, the Harold Brunn Institute for Cardiovascular Research, San Francisco, Calif. The distribution of digitoxin in various organs and tissues of the rat, rabbit and dog was studied after parenteral administration of the glycoside. Digitoxin when given intravenously to the rat (1 mcg./gm. of body weight) was found to enter all organs and tissues assayed (liver, kidney, heart, brain, lung, spleen and muscle) except the brain. The hepatic content of digitoxin immediately after injection (6.3 mcg./gm.) was three times that of the heart (2.0 mcg./gm.), the latter organ having approximately the same amount of digitoxin as the lung and kidney. Digitoxin content of these organs gradually decreased following injection but the liver of the rat continued to have much more digitoxin than any other organ or tissue assayed. Approximately three hours after injection the brain for the first time was found to contain digitoxin. Ten hours after injection the liver was found to contain twenty times as much digitoxin (1.2 mcg./gm.) as the lung, the heart or skeletal muscle. At this time the brain was found to contain three times as much digitoxin as the heart. Sixteen hours after injection only the liver and brain were found to contain detectable amounts of digitoxin (i.e., quantities of 0.05 mcg. or above). At the end of twenty-four hours no tissue was found to contain significant amounts of digitoxin. Similar distribution of digitoxin was found in the organs and tissues of the rabbit and dog except that the liver of either of these species did not seem to concentrate digitoxin as did that of the rat, although a considerable concentration of digitoxin was found to be present in the medullary area of the kidney of these two species. USE OF AUREOMYCIN IN THE TREATMENT OF CONGENITAL FIBROCYSTICDISEASE. Henry B. Bruyn, Division of Pediatrics, University of California Medical School, and the Infectious AMERICAN
JOURNAL
OF
MEDICINE
Western Society for Clinical Research Disease Laboratory of the San Francisco City and County Hospital, San Francisco, Calif. The major problem in the treatment of children with fibrocystic disease of the lungs and pancreas has been to control the repeated pulmonary infections which remain the principal cause of death. Antibiotics have prolonged the lives of these children and recently aureomycin has been reported to have value in the treatment and prophylaxis of pulmonary infections. The present study involves the use of aureomycin, over a period ranging from two to eighteen months, in twenty-eight proved cases of fibrocystic disease. All children had the constant cough characteristic of the pulmonary infection associated with this disease. All children were placed on a dosage of 125 mg. of aureomycin given twice a day. Of these twenty-eight children five required increasing amounts of drug at intervals throughout the course of the study when the cough reappeared or increased in frequency. Weight gain and appetite were improved during aureomycin therapy in most instances. In seven children in whom aureomycin therapy was instituted within four months of the onset of symptoms of this disease, the course approximates that of a normal child. Five children died during therapy, two of these deaths attributable to fibrocystic disease alone. Twenty-four of the twenty-eight children had good results, with either marked diminution or complete disappearance of the cough characteristic of this disease. Only one child has not tolerated the drug and has required other therapy. Two rashes, due to aureomycin, have necessitated a change to another antibiotic. Blood levels of aureomycin ranged between 1 to 5 micrograms/cc. of serum taken four hours after the last dose of drug and determined over a period of from one to six months of therapy. Throat and rectal bacterial flora changed very little qualitatively, but seemed to diminish quantitatively over the course of the study. Sensitivity to aureomycin was determined on all species of bacteria found in the throat and rectum at varying intervals of therapy. Sensitive as well as relatively resistant strains were found irrespective of blood level or duration of therapy. It is concluded that up to the present time daily aureomycin is most effective in the management of congenital fibrocystic disease.
EXPERIMENTALPRODUCTION OFNODALRHYTHMS IN HUMAN SUBJECTS.Merrill C. Daines and JUNE,
1951
773
of Medicine, Hans H. Hecht,* Department University of Utah College of Medicine, Salt Lake City, Utah. The observations by Wilson (1915) that the atrioventricular node of the normal human heart is released from the effects of vagal stimulation before the sinus node has led to the experimental production of abnormal auriculai rhythms in normal young adults. Twenty-five subjects (age twenty-two to received 1 mg. neosynephrine thirty-four) hydrochloride by vein. The peripheral effects of this sympathomimetic compound outweigh its cardiac action and, therefore, an abrupt rise in peripheral resistance without cardiac acceleration occurs immediately upon the injection. This is followed promptly by vagal reflex suppression of sinus activity with pronounced bradycardia and is characterized by the appearance of abnormal, slow, supraventricular rhythms, often preceded or followed by periods of excessive PR prolongation and auricular standstill. Various types of “coronary sinus” and atrioventricular nodal rhythms occurred lasting up to two minutes in twenty-three of the twenty-five subjects. Shifting of the abnormal pacemaker within the node occurred seven times. The chain of events can be blocked by dibenamine and by atropine and can be interrupted by amyl nitrite. The ventricular complexes of the nodal beats showed almost invariably some alteration in form, suggesting that vagal stimulation may influence impulse conduction over ventricular tissue. The technic is useful for a number of clinical and physiologic problems.
CLINICAL TRIAL OF DIPHENHYDRAMINE IN AuRICULAR FIBRILLATION. H. Lenox, H. Dick and Elton L. McCawley, Department of Pharmacology, University of Oregon Medical School, Portland, Ore. Laboratory studies show that diphenhydramine resembles quinidine in its ability to prolong the refractory period of the isolated auricle, to elevate the threshold of the myocardium to electrical stimulation, to exhibit an antivagal action, and to convert induced auricular fibrillation and flutter in dogs or rabbits to normal rhythm. A mild atropine-like action and a synergistic action with epinephrine also has been observed. Toxicity studies in dogs indicate no serious untoward cardiac effects. We have compared the antifibrillatory action of diphenhydramine with quinidine in twelve patients with
and flow tide of white blood cells into and out of the circulation can occur rapidly and is influenced by respirations. These findings support the original contention that the pulmonary circulation contains a potent mechanism for controlling the leukocyte level in the peripheral blood in man. Further implications will be discussed. DISTRIBUTIONOF DICITOXIN IN THE ANIMAL BODY AFTER ITS PARENTERALADMINISTRATION.Reni Bine, Jr., Meyer Friedman, * and Sanford 0. Byers. Mount Zion Hospital, the Harold Brunn Institute for Cardiovascular Research, San Francisco, Calif. The distribution of digitoxin in various organs and tissues of the rat, rabbit and dog was studied after parenteral administration of the glycoside. Digitoxin when given intravenously to the rat (1 mcg./gm. of body weight) was found to enter all organs and tissues assayed (liver, kidney, heart, brain, lung, spleen and muscle) except the brain. The hepatic content of digitoxin immediately after injection (6.3 mcg./gm.) was three times that of the heart (2.0 mcg./gm.), the latter organ having approximately the same amount of digitoxin as the lung and kidney. Digitoxin content of these organs gradually decreased following injection but the liver of the rat continued to have much more digitoxin than any other organ or tissue assayed. Approximately three hours after injection the brain for the first time was found to contain digitoxin. Ten hours after injection the liver was found to contain twenty times as much digitoxin (1.2 mcg./gm.) as the lung, the heart or skeletal muscle. At this time the brain was found to contain three times as much digitoxin as the heart. Sixteen hours after injection only the liver and brain were found to contain detectable amounts of digitoxin (i.e., quantities of 0.05 mcg. or above). At the end of twenty-four hours no tissue was found to contain significant amounts of digitoxin. Similar distribution of digitoxin was found in the organs and tissues of the rabbit and dog except that the liver of either of these species did not seem to concentrate digitoxin as did that of the rat, although a considerable concentration of digitoxin was found to be present in the medullary area of the kidney of these two species. USE OF AUREOMYCIN IN THE TREATMENT OF CONGENITAL FIBROCYSTICDISEASE. Henry B. Bruyn, Division of Pediatrics, University of California Medical School, and the Infectious AMERICAN
JOURNAL
OF
MEDICINE
Western Society for Clinical Research Disease Laboratory of the San Francisco City and County Hospital, San Francisco, Calif. The major problem in the treatment of children with fibrocystic disease of the lungs and pancreas has been to control the repeated pulmonary infections which remain the principal cause of death. Antibiotics have prolonged the lives of these children and recently aureomycin has been reported to have value in the treatment and prophylaxis of pulmonary infections. The present study involves the use of aureomycin, over a period ranging from two to eighteen months, in twenty-eight proved cases of fibrocystic disease. All children had the constant cough characteristic of the pulmonary infection associated with this disease. All children were placed on a dosage of 125 mg. of aureomycin given twice a day. Of these twenty-eight children five required increasing amounts of drug at intervals throughout the course of the study when the cough reappeared or increased in frequency. Weight gain and appetite were improved during aureomycin therapy in most instances. In seven children in whom aureomycin therapy was instituted within four months of the onset of symptoms of this disease, the course approximates that of a normal child. Five children died during therapy, two of these deaths attributable to fibrocystic disease alone. Twenty-four of the twenty-eight children had good results, with either marked diminution or complete disappearance of the cough characteristic of this disease. Only one child has not tolerated the drug and has required other therapy. Two rashes, due to aureomycin, have necessitated a change to another antibiotic. Blood levels of aureomycin ranged between 1 to 5 micrograms/cc. of serum taken four hours after the last dose of drug and determined over a period of from one to six months of therapy. Throat and rectal bacterial flora changed very little qualitatively, but seemed to diminish quantitatively over the course of the study. Sensitivity to aureomycin was determined on all species of bacteria found in the throat and rectum at varying intervals of therapy. Sensitive as well as relatively resistant strains were found irrespective of blood level or duration of therapy. It is concluded that up to the present time daily aureomycin is most effective in the management of congenital fibrocystic disease.
EXPERIMENTALPRODUCTION OFNODALRHYTHMS IN HUMAN SUBJECTS.Merrill C. Daines and JUNE,
1951
773
of Medicine, Hans H. Hecht,* Department University of Utah College of Medicine, Salt Lake City, Utah. The observations by Wilson (1915) that the atrioventricular node of the normal human heart is released from the effects of vagal stimulation before the sinus node has led to the experimental production of abnormal auriculai rhythms in normal young adults. Twenty-five subjects (age twenty-two to received 1 mg. neosynephrine thirty-four) hydrochloride by vein. The peripheral effects of this sympathomimetic compound outweigh its cardiac action and, therefore, an abrupt rise in peripheral resistance without cardiac acceleration occurs immediately upon the injection. This is followed promptly by vagal reflex suppression of sinus activity with pronounced bradycardia and is characterized by the appearance of abnormal, slow, supraventricular rhythms, often preceded or followed by periods of excessive PR prolongation and auricular standstill. Various types of “coronary sinus” and atrioventricular nodal rhythms occurred lasting up to two minutes in twenty-three of the twenty-five subjects. Shifting of the abnormal pacemaker within the node occurred seven times. The chain of events can be blocked by dibenamine and by atropine and can be interrupted by amyl nitrite. The ventricular complexes of the nodal beats showed almost invariably some alteration in form, suggesting that vagal stimulation may influence impulse conduction over ventricular tissue. The technic is useful for a number of clinical and physiologic problems.
CLINICAL TRIAL OF DIPHENHYDRAMINE IN AuRICULAR FIBRILLATION. H. Lenox, H. Dick and Elton L. McCawley, Department of Pharmacology, University of Oregon Medical School, Portland, Ore. Laboratory studies show that diphenhydramine resembles quinidine in its ability to prolong the refractory period of the isolated auricle, to elevate the threshold of the myocardium to electrical stimulation, to exhibit an antivagal action, and to convert induced auricular fibrillation and flutter in dogs or rabbits to normal rhythm. A mild atropine-like action and a synergistic action with epinephrine also has been observed. Toxicity studies in dogs indicate no serious untoward cardiac effects. We have compared the antifibrillatory action of diphenhydramine with quinidine in twelve patients with