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A correlation of the spatial vectorcardiogram with right ventricular hypertrophy
Western Society for Clinical Research decreases of steroid concentration occurred when the salicylate level was low; fluctuations and elevations when it was considerably elevated, usually above 25 mg. per cent. Moreover, subjects given low salicylate doses consistently showed a decrease in 17-hydroxycorticosteroid concentrations. The inconsistent increases in 17-hydroxycorticosteroid concentrations in response to single high salicylate doses, the consistent decreases in response to single low doses, and the marked fluctuations in responses to repeated doses suggest the possibility that salicylates cause both an increased peripheral utilization and an increased secretion of 17hydroxycorticosteroids. Animal experiments designed to clarify the interpretation of these data are in progress. THE ADRENAL RESPONSETO BACTERIAL PYROGENS.Kristen Eik-Nes and Leo T. Samuels, * Dept. of Biochemistry, Univ. of Utah College of Medicine, Salt Lake City, Utah. The changes in concentration of 17-hydroxycorticosteroids have been studied in the peripheral blood of dogs and humans following the injection of various doses of partially purified bacterial pyrogen from Pseudomonas. The levels in the adrenal venous blood have also been followed in the dog. Immediately after injection of the pyrogen the levels of cortical steroids rose. The concentration reached a peak at thirty-sixty minutes and then receded. The temperature change did not begin as soon as that of the steroids, and the most rapid rise was often after the steroid concentration had passed its peak. When ACTH was given at this time there was a further rise in the 17-hydroxycorticosteroids, associated with a temporary depression of the temperature rise. The same effect could be produced by intravenous injection of hydrocortisone or even by a second injection of pyrogen. In the latter case there was generally a rapid rise in temperature after the second rise in steroid concentration had passed its peak. It would seem that introduction of pyrogen leads to a discharge of adrenal steroids which depends on the immediate presence of the toxic compound and not on the febrile response. A CORRELATIONOF THE SPATIAL VECTORCARDIOGRAMWITH RIGHT VENTRICULARHYPERTROPHY. Stephen R. Elek, * Bertram J. Allenstein, and George C. Grz$th,* Dept. of Medicine, Univ. of Southern California, Los Angeles, Calif. SEPTEMBER,
1953
4’3
Using direct oscilloscopic vectorcardiography and the Duchosal-Sulzer cube arrangement, Grishman et al. have shown that the spatial vectocardiogram in right ventricular hypertrophy is shifted to the right ante$or octant. Grishman has correlated the QRS SE loop with right ventricular pressure but only in congenital heart disease. We have correlated the spatial vectorcardiogram in congenital and acquired heart disease (mitral stenosis) with both mean right ventricular systolic ejection pressure and right ventricular work. We have also compared the vectorcardiogram with the electrocardiogram in both lesions. Thirty-four patients (sixteen with mitral stenosis and eighteen with congenital heart disease) were chosen. The basis of selection was the presence of “isolated” right ventricular hypertrophy demonstrated by cardiac catheterization. Patients with clinical evidence of left ventricular hypertrophy were not included. Right ventricular work was determined by the formula of Gorlin; values above 1.0 Kg. M/ min./sq.M. (hereinafter referred to as “units”) were considered abnormal. In both lesions combined there were twenty-five patients with right ventricular work greater than 1.06 “units” and nine with right ventricular work less than 1.06 “units.” We have confirmed the increasing rightward deviation of the horizontal plane loop with right ventricular work above normal. The degree of rightward shift of the spatial vectorcardiogram was well correlated in twenty-two of the twenty-five patients with elevated right ventricular work. The data show that there is a closer correlation between the vectorcardiogram and right ventricular work than there is between the electrocardiogram and right ventricular work. The electrocardiogram showed evidence of right ventricular hypertrophy in only thirteen of the twenty-five patients with right ventricular work above normal; nine of these patients had partial right bundle branch block. Vectorcardiographic evidence is offered that partial right bundle branch block does represent right ventricular hypertrophy. The data indicate that the vectorcardiogram clearly shows the existence of right ventricular hypertrophy while the electrocardiographic evidence of right ventricular hypertrophy is often obscured by the presence of partial right bundle branch block.
414
Western
Society for Clinical Research
The vectorcardiogram, at least in congenital heart disease, may serve as a gross quantitative estimate of the degree of right ventricular hypertrophy and this can influence the preoperative decision. DISTRIBUTION AND FATE OF INSULININ NORMALS AND IN SUBJECTSWITH VARIOUS LEVELS OF FUNCTIONOF THE PITUITARY, THYROID, ADRENAL, PANCREASAND LIVER. Neil J. Elgee and
Robert H. Williams, * Dept. of Medicine, Univ. of Washington School of Medicine, Seattle, Wash. Highly purified crystalline insulin was labeled with 1131 using the method of Ferrebee et al. (Endocrinology, 48: 277, 1951). The radioactivity could not be dialyzed away and did not move from the baseline on paper chromatograms using an acid-butanol solvent. The physiologic activity of the labeled insulin as measured by glucose uptake of the rat diaphragm was unimpaired. The material was given intravenously to patients with diabetes, cirrhosis, uremia, thyrotoxicosis, myxedema, Addison’s disease and hyperinsulinism, and the radioactivity in blood and urine followed. Distribution and time studies in the rat were carried out following intravenous administration of the labeled insulin. In normal rats the radioactivity was very highly concentrated in kidney and liver, less in spleen and blood, and much less per unit mass in muscle, fat, thyroid, pancreas, testes, adrenals, pituitary and brain. No significant amount was found in the red blood cells. The effect of growth hormone, compound F, growth hormone plus compound F, thyroxine, insulin and the hyperglycemic factor on the distribution in normal, hypophysectomized and adrenalectomized rats and the effect of thyroidectomy and alloxan diabetes on the distribution of the radioactivity was studied. The results of these experiments and some of their implications with respect to disorders of carbohydrate metabolism observed clinically will be discussed. STUDY OF THE EFFECTSOF PHENYLBUTAZONE IN THE TREATMENTOF GOUT. Ephraim P. Engleman, * Marcus A. Krupp, * Peter Forsham, A. Clark Grajin, Harold Johnson, Thomas Green and Alan Goldjen, San Francisco Veterans Administration Hospital, Univ. of California School of Medicine, Stanford University Medical School, San Francisco, Calif.
Twenty-five male patients with acute gouty arthritis have been treated with phenylbutazone during the past year. In general the results have been excellent, with rapid, often dramatic, recovery. Ten of these patients had had recurrent gouty arthritis at regular intervals for years prior to the administration of phenylbutazone. Upon continuous treatment with adequate doses of the drug the cyclic recurrences of gout have not occurred, suggesting prophylactic value of the drug. The incidence of toxicity was high, necessitating cessation of the drug in one patient. Four patients were subjects of careful study in an effort to discern the mechanism of action of phenylbutazone. The drug caused a striking decrease in the blood uric acid, despite failure to demonstrate an uricosuric effect. The urinary excretion of compound F-like substances in the urine was significantly decreased. Preliminary studies have shown that phenylbutazone markedly enhances the P32 incorporation and turnover in liver tissue nucleic acid or nucleoprotein. STUDIES ON MORPHOLOGIC ALTERATIONSON HUMAN LYMPHOCYTES. Jules A. Frank and
Thomas F. Dougherty,* Dept. of Anatomy, Univ. of Utah, Salt Lake City, Utah. Previous investigations in this laboratory on circulating lymphocytes of mice demonstrate that normal lymphocytes (numerically and morphologically) represent a balance between: (1) adrenocortical hormone influence (lymphopenia with morphologic alterations of pycnosis, cytoplasmic budding and karyorrhexis); and (2) a non-adrenocortically mediated influence (lymphocytosis and/or the morphologic alterations of hyalinization of cytoplasm and increased cytoplasmic-nuclear ratio). Morphologically, circulating lymphocytes of stressed, adrenalectomized mice resemble the type II lymphocyte of Downey. Observations on lymphocytes of normal subjects, normal subjects given ACTH and normal subjects given epinephrine were made and correlated with blood hydrocorticosteroid levels. Ten normal subjects given 15 mg. of ACTH intravenously exhibited a lymphopenia of normal lymphocytes at four hours anticipated by a rise in blood hydrocorticosteroids. Type II lymphocytes did not vary significantly from their control levels. Two normal subjects given 3.0 mg. epinephrine by infusion over four hours AMERICAN
JOURNAL
OF
MEDICINE
1953
4’3
Using direct oscilloscopic vectorcardiography and the Duchosal-Sulzer cube arrangement, Grishman et al. have shown that the spatial vectocardiogram in right ventricular hypertrophy is shifted to the right ante$or octant. Grishman has correlated the QRS SE loop with right ventricular pressure but only in congenital heart disease. We have correlated the spatial vectorcardiogram in congenital and acquired heart disease (mitral stenosis) with both mean right ventricular systolic ejection pressure and right ventricular work. We have also compared the vectorcardiogram with the electrocardiogram in both lesions. Thirty-four patients (sixteen with mitral stenosis and eighteen with congenital heart disease) were chosen. The basis of selection was the presence of “isolated” right ventricular hypertrophy demonstrated by cardiac catheterization. Patients with clinical evidence of left ventricular hypertrophy were not included. Right ventricular work was determined by the formula of Gorlin; values above 1.0 Kg. M/ min./sq.M. (hereinafter referred to as “units”) were considered abnormal. In both lesions combined there were twenty-five patients with right ventricular work greater than 1.06 “units” and nine with right ventricular work less than 1.06 “units.” We have confirmed the increasing rightward deviation of the horizontal plane loop with right ventricular work above normal. The degree of rightward shift of the spatial vectorcardiogram was well correlated in twenty-two of the twenty-five patients with elevated right ventricular work. The data show that there is a closer correlation between the vectorcardiogram and right ventricular work than there is between the electrocardiogram and right ventricular work. The electrocardiogram showed evidence of right ventricular hypertrophy in only thirteen of the twenty-five patients with right ventricular work above normal; nine of these patients had partial right bundle branch block. Vectorcardiographic evidence is offered that partial right bundle branch block does represent right ventricular hypertrophy. The data indicate that the vectorcardiogram clearly shows the existence of right ventricular hypertrophy while the electrocardiographic evidence of right ventricular hypertrophy is often obscured by the presence of partial right bundle branch block.
414
Western
Society for Clinical Research
The vectorcardiogram, at least in congenital heart disease, may serve as a gross quantitative estimate of the degree of right ventricular hypertrophy and this can influence the preoperative decision. DISTRIBUTION AND FATE OF INSULININ NORMALS AND IN SUBJECTSWITH VARIOUS LEVELS OF FUNCTIONOF THE PITUITARY, THYROID, ADRENAL, PANCREASAND LIVER. Neil J. Elgee and
Robert H. Williams, * Dept. of Medicine, Univ. of Washington School of Medicine, Seattle, Wash. Highly purified crystalline insulin was labeled with 1131 using the method of Ferrebee et al. (Endocrinology, 48: 277, 1951). The radioactivity could not be dialyzed away and did not move from the baseline on paper chromatograms using an acid-butanol solvent. The physiologic activity of the labeled insulin as measured by glucose uptake of the rat diaphragm was unimpaired. The material was given intravenously to patients with diabetes, cirrhosis, uremia, thyrotoxicosis, myxedema, Addison’s disease and hyperinsulinism, and the radioactivity in blood and urine followed. Distribution and time studies in the rat were carried out following intravenous administration of the labeled insulin. In normal rats the radioactivity was very highly concentrated in kidney and liver, less in spleen and blood, and much less per unit mass in muscle, fat, thyroid, pancreas, testes, adrenals, pituitary and brain. No significant amount was found in the red blood cells. The effect of growth hormone, compound F, growth hormone plus compound F, thyroxine, insulin and the hyperglycemic factor on the distribution in normal, hypophysectomized and adrenalectomized rats and the effect of thyroidectomy and alloxan diabetes on the distribution of the radioactivity was studied. The results of these experiments and some of their implications with respect to disorders of carbohydrate metabolism observed clinically will be discussed. STUDY OF THE EFFECTSOF PHENYLBUTAZONE IN THE TREATMENTOF GOUT. Ephraim P. Engleman, * Marcus A. Krupp, * Peter Forsham, A. Clark Grajin, Harold Johnson, Thomas Green and Alan Goldjen, San Francisco Veterans Administration Hospital, Univ. of California School of Medicine, Stanford University Medical School, San Francisco, Calif.
Twenty-five male patients with acute gouty arthritis have been treated with phenylbutazone during the past year. In general the results have been excellent, with rapid, often dramatic, recovery. Ten of these patients had had recurrent gouty arthritis at regular intervals for years prior to the administration of phenylbutazone. Upon continuous treatment with adequate doses of the drug the cyclic recurrences of gout have not occurred, suggesting prophylactic value of the drug. The incidence of toxicity was high, necessitating cessation of the drug in one patient. Four patients were subjects of careful study in an effort to discern the mechanism of action of phenylbutazone. The drug caused a striking decrease in the blood uric acid, despite failure to demonstrate an uricosuric effect. The urinary excretion of compound F-like substances in the urine was significantly decreased. Preliminary studies have shown that phenylbutazone markedly enhances the P32 incorporation and turnover in liver tissue nucleic acid or nucleoprotein. STUDIES ON MORPHOLOGIC ALTERATIONSON HUMAN LYMPHOCYTES. Jules A. Frank and
Thomas F. Dougherty,* Dept. of Anatomy, Univ. of Utah, Salt Lake City, Utah. Previous investigations in this laboratory on circulating lymphocytes of mice demonstrate that normal lymphocytes (numerically and morphologically) represent a balance between: (1) adrenocortical hormone influence (lymphopenia with morphologic alterations of pycnosis, cytoplasmic budding and karyorrhexis); and (2) a non-adrenocortically mediated influence (lymphocytosis and/or the morphologic alterations of hyalinization of cytoplasm and increased cytoplasmic-nuclear ratio). Morphologically, circulating lymphocytes of stressed, adrenalectomized mice resemble the type II lymphocyte of Downey. Observations on lymphocytes of normal subjects, normal subjects given ACTH and normal subjects given epinephrine were made and correlated with blood hydrocorticosteroid levels. Ten normal subjects given 15 mg. of ACTH intravenously exhibited a lymphopenia of normal lymphocytes at four hours anticipated by a rise in blood hydrocorticosteroids. Type II lymphocytes did not vary significantly from their control levels. Two normal subjects given 3.0 mg. epinephrine by infusion over four hours AMERICAN
JOURNAL
OF
MEDICINE