Milton Mendlowitz

A quantitative assay for vanillylmandelic acid (VMA) by gas-liquid chromatography

A quantitative assay for vanillylmandelic acid (VMA) by gas-liquid chromatography / Sherwin Wilk From the Department of Medicine, th eMount Sinai Hospital, New York, New York and the Department of Chemistry, Fordham University, New York, N.Y. Stanley E. Gitlow and Milton Mendlowitz From the Department of Medicine, The Mount Sinai Hospital, New York, New York Morton J. Franklin and Herman E. Carr From the Department of Psychiatry, Boston University, School of Medicine, Boston, Massachusetts and Donald D. Clarke From the Department of

The experimental simulation in the dog of the cyanosis and hypertrophic osteoarthropathy which are associated with congenital heart disease

Abstract 1. 1. A procedure for anastomosis of the pulmonary artery to the left auricle in dogs is described. 2. 2. In the successful experiments, this procedure reproduced the circulatory derangements found in the cyanotic type of congenital heart disease. 3. 3. In one experiment, hypertrophic osteoarthropathy developed, and was apparently attributable to increased systemic blood flow.

THE EFFECT OF CHLOROTHIAZIDE AND ITS CONGENERS ON THE DIGITAL CIRCULATION IN NORMOTENSIVE SUBJECTS AND IN PATIENTS WITH ESSENTIAL HYPERTENSION

The action of chlorothiazide or its congeners on the circulation is not clearly understood. It is known, for example, that these drugs can reduce the blood pressure of patients with essential hypertension and yet have no effect on the blood pressure of normal and also that they increase the antihypertensive effect of other drugs such as the ganglion blocker^.^-^ Chlorothiazide decreases the plasma volume* and the cardiac outputa of patients with hypertension; later, when plasma volume and cardiac output return to normal, blood pressure is still kept low by the druglo It has also been shown that pressor response to injected &norepinephrine (NE) is decreased in normotensive as well as in hypertensive1*J3 subjects by chlorothiazide. The results, however, are not always clear-cut and there is much overlapping. Most workers agree that the circulatory effects are secondary to the direct action of chlorothiazide on the kidney, with resultant loss of sodium and potassium chloride and water, 5 ~ 1 4 whereas others believe that the drug may have some additional direct action on the tissues and systemic blood vessels? In order to clarify some of these questions, a study was undertaken in both normotensive and hypertensive subjects of the effect of these drugs on the digital circulation. Several factors could thus be studied concomitantly by established meth0ds.~-7 Studies were completed on nine normotensive and ten hypertensive subjects before and after the administration of chlorothiazide at a dosage of 500 mg. twice daily for two weeks. Similar studies were carried out in four normotensive and four hypertensive subjects on hydrochlorothiazide (50 mg. twice daily for two weeks), and in three normotensive and three hypertensive subjects on benzydroflumethiazide (5 mg. twice daily for two weeks). At each session, brachial and digital blood pressures and digital blood flow were measured in three phases: (1) in the resting state under standardized conditions, including maintenance of room temperature between 26 and 29 C. (phase B); (2) after vasodilatation produced by indirect heating with a cradle baker over the trunk until positive heat balance was manifested by profuse diaphoresis, followed by the intravenous administration of 0.8 mg./kg. of SC 1950 (2,6-dimethyl-l , 1diethyl piperidiniurn bromide), a ganglion-blocking drug (phase A) ; and (3) with the conditions in phase A remaining constant during the intravenous infusion of NE and additional SC 1950 at a rate sufficient to bring the subjects blood pressure to its original value or somewhat higher (phase C). The in-

Vascular reactivity in essential and renal hypertension in man

Abstract 1. 1. Vascular reactivity in man has been studied under many different conditions with a variety of methods. 2. 2. The most productive methods employ either intra-arterial or intravenous infusion after inhibition of sympathetic nerve discharge, and interpret changes in flow and pressure in terms of work of vasoconstriction rather than resistance. 3. 3. With the use of such methods, vascular reactivity to various substances, including 1-norepinephrine (NE) and angiotensin II (AT), has been found to be increased in essential hypertension but not in various types of renal hypertension. Other methods have yielded equivocal and ofter contradictory results. 4. 4. Reactivity in the digit measured by the work method can be decreased in essential hypertensive patients by salt depletion, with a variable effect in normotensive subjects. Guanethidine and alpha-methyldopa increase reactivity, although they decrease blood pressure. Glucocorticosteroids increase reactivity in normotensive subjects but not in patients with essential hypertension, whereas aldosterone and salt increase reactivity, particularly in the hypertensive group and only slightly in the normotensive group. 5. 5. Evidence is accumulating to implicate the renin-angiotensin system in renovascular and accelerated essential hypertension with nephrosclerosis. In hypertension secondary to various types of parenchymatous renal disease, immune reactions in the blood vessels seem to be involved. Other theories are discussed.

Diagnosis of Pheochromocytoma by Assay of Catecholamine Metabolites

Methods for the determination of urinary vanillylmandelic acid (VMA) have been reviewed and variations in VMA excretion in different disease states summarized. The determination of VMA excretion is believed to represent a reliable method for the detection of a pheochromocytoma. Colorimetric screening tests for the detection of elevated VMA excretion have been reviewed and evaluated as laboratory aids in the diagnosis of pheochromocytoma.

The carotid sinus reflexes

Abstract Forty years have elapsed since Hering defined the carotid sinus reflex. Present theory indicates that the reflexes act by “buffering” the outflow from the brain of sympathetic and parasympathetic nervous system activity. Through changes in this autonomic nervous system outflow, decreases in systemic arterial pressure would be opposed by (a) decreases in the distensibility and volume of the systemic postarteriolar capacity vessels, (b) increases in cardiac work, and (c) increases in total peripheral resistance. Conversely, increases in arterial pressure would be opposed by effects in the opposite direction. Until the last decade, baroreceptor experimental neurogenic hypertension was produced by bilateral carotid sinus denervation and partial vagotomy. The hypertension so caused was singularly unlike essential hypertension. It was very labile, and the increase in arterial pressure was associated with tachycardia and an elevation of cardiac output. However, since 1954, it has been clearly demonstrated that permanent, stable hypertension without tachycardia can readily be produced in dogs by bilaterally interfering with the carotid sinus reflexes alone (vagi intact). Furthermore, it has been shown that the carotid sinus reflexes may be of significance in the production of renal hypertension. Also, carotid sinus pacemakers have recently been shown to be capable of reducing blood pressure in hypertensive dogs and man. It has been held for more than 30 years that spontaneous syncopal attacks are caused by stimulation of the carotid sinus reflexes. Nevertheless, in the great majority of patients with a diagnosis of carotid sinus syndrome, spontaneous syncope is not associated with an immediately apparent stimulation of the carotid sinus, such as direct pressure, a tight collar, shaving, or scratching. It is argued in the present communication that in those cases without apparent stimulation of the carotid sinus the diagnosis of carotid sinus syndrome cannot be made or classified by the tests presently employed. Even the results of surgical denervation cannot prove the existence of the carotid sinus syndrome in most cases.

The effect of spironolactone on digital vascular reactivity in essential hypertension

Abstract 1. 1. Spironolactone was administered (100 mg. daily) to 16 hypertensive patients for 2 weeks. 2. 2. Brachial and digital blood pressures and digital blood flow (calorimetric) were measured before and after vasodilatation by indirect heat supplemented by ganglion blockade, as well as during the intravenous administration of l-norepinephrine (NE). These measurements were made before and at the end of the drug period and from the data, changes in digital vascular caliber and work of vasoconstriction were calculated. 3. 3. The drug produced a statistically significant decrease in supine brachial and digital blood pressure and in digital vascular reactivity to NE. 4. 4. These decreases seem attributable to sodium depletion by the drug.

The effect of aldosterone on electrolytes and on digital vascular reactivity to I-norepinephrine in normotensive, hypertensive, and hypotensive subjects☆

Abstract 1. 1. Aldosterone was administered intramuscularly to 15 normotensive subjects and 15 patients with essential hypertension who were on a fixed intake of sodium chloride. Two patients with renal hypertension and 2 with postural hypotension were also studied. 2. 2. The excretion of sodium in the urine was significantly decreased in the normotensive group. The other electrolyte changes were inconclusive. 3. 3. Digital vascular responsiveness to 1-norepinephrine was significantly increased from an initially high level by the aldosterone in the subjects with essential hypertension but only slightly increased in the normotensive subjects. It was also found to increase from an initially normal level in the 2 patients with renal hypertension, and to decrease from an initially high level in the 2 patients with postural hypotension. 4. 4. The possible mechanisms involved in these changes are discussed.

Metabolism of Corticotropin in Man.

Summary Synthetic beta1-24 corticotropin has been labeled with I131 and intravenously administered to normal subjects. Analysis of the blood radioactivity following intravenous administration of beta1-24 corticotropin-I131 revealed that this substance has an apparent space of distribution of 43% of the body weight and a plasma half-life of 7 minutes.

Digital vascular reactivity to L-norepinephrine in the second trimester of pregnancy as a test for latent essential hypertension and toxemia.

I N 1 9 5 7 1 neurogenic vasoconstriction was estimated quantitatively by measuring blood pressure and blood flow in the digit under standardized conditions of rest and room temperature and again after vasodilatation by indirect heat supplemented by the intravenous injection of a ganglion-blocking drug. These data were converted to radius equivalents by means of PoiseuiIles law ancl from these radius equivalents and the pressures the physical work performed by the smooth muscle of the blood vessels in changing one steady state (vasodilatation) to another (vasoconstriction) was calculated. With these methods, neurogenic vasoconstriction was demonstrated to be increased over normal values in essential hypertension. A similar procedure was subsequently applied to estimating vascular reactivity to L-norepinephrine (NE) by measuring the work of vasoconstriction produced by digital vascular smooth muscle in response to a fixed rate of infusion of NE.2 Such reactivity was found to be strikingly and uniformly increased in essential hypertension.