Search

Propylthiouracil is generally conceded to be the least toxic antithyrotoxic agent at the moment. Serious reactions to this drug are almost lacking in the literature. Reports of two febrile and urticarial reactions in 129 cases 1 and of 1 case of leukopenia and sore throat in a series of 110 cases 2 have appeared. Astwood and VanderLaan have now treated over 100 patients without the development of any significant side effect. 3 In 260 patients treated with the drug at the Lahey Clinic depression of the white blood cell count has been noticed in 5 instances. 4 The development of pronounced leukopenia in a patient under treatment with this drug was therefore considered of sufficient importance to report. A second point of interest in the case is the increasing degree of thyrotoxicosis that developed while propylthiouracil was being administered in what was thought to be an adequate maintenance dose. REPORT

Procaine amide, a new synthetic analogue of procaine, has marked antiarrythmic activity and is relatively stable in the body. It is effective when administered orally or intravenously, and has few toxic effects in therapeutic doses. The drug has been used successfully in the suppression of ventricular premature contractions and in the interruption of ventricular tachycardia. Some patients treated successfully with procaine amide had been given quinidine to the point of toxicity without affecting the aberrant rhythm. Procaine amide appears to be less effective in interrupting auricular than ventricular arrhythmias.

Summary In sumary, then, bronchial compression by an enlarged left auricle has been known to occur for nearly a century. It is known also that due to this cause compression does occasionally cause morbid changes in the lung, recognizable clinically. The knowledge of this phenomenon may be of use in explaining persistent pulmonary signs otherwise puzzling. At present I believe that compression and displacement of the left bronchus are much more common in mitral disease than is supposed, but only infrequently are they great enough to give rise to secondary lung changes, such as bronchiectasis, chronic basilar infections, and atelectasis. I hope shortly to show that it may also be demonstrated by x-ray examination when no pulmonary signs exist. The present case gave no evidence of bronchiectasis by x-ray examination, but the bronchial tree was outlined and the compression and displacement of the left main bronchus were apparent. This explains readily the persistence of the expectoration of sputum and of the abnormal pulmonary signs at the left base alone.

1. 1. It is well known that a considerable portion of the variation in arterial pulse wave velocity as measured in living individuals is due to size and thickness of wall, and to pressure within the walls, as well as to actual changes in elasticity of the wall itself. When an index of the elasticity of the arterial wall is sought by measuring pulse wave velocity, the error due to size and thickness of the wall can in part be taken into account only by measurements carried out upon the same artery; that due to pressure can be largely accounted for by individual relationships found to exist between speed of the pulse wave and pressure. 2. 2. The pressure upon which the speed is dependent is not systolic, mean or pulse pressure but unequivocally diastolic pressure. The logical argument for this conclusion is supported by studies of pulse wave velocity carried out in dogs in which the levels of systolic and diastolic pressures were varied independently. The velocity of the pulse wave was not affected by variations in systolic pressure alone and hence neither by mean or pulse pressure. Changes in diastolic pressure only were regularly accompanied by changes in pulse wave velocity. 3. 3. When the effect of the higher diastolic pressures occurring in hypertensive individuals without obvious arteriosclerosis is taken into account, it seems that the elastic properties and, inferentially, the tone of the muscular coats, of the larger arteries behave like those of normal ones.

1. 1. A case of heart failure is reported exhibiting Cheyne-Stokes respiration in which various types of cardiac arrhythmia were recurrently manifested during the dyspneic phases of the respiratory cycle. 2. 2. Sinus slowing, prolongation of the P-R interval, partial and complete heart-block, and during suppression of the formation of sinus impulses, idiopathic ventricular rhythms were observed. 3. 3. All of these changes in rhythm have previously been observed to follow various degrees of vagal stimulation. 4. 4. With the exception of sinus slowing, all the phenomena occurred only after administration of digitalis in effective therapeutic doses. 5. 5. Since digitalis has usually been administered in cases of Cheyne-Stokes breathing in which such disturbances of rhythm appeared during the dyspneic phase, it is suggested that the vagal effec of this drug is a powerful adjunct in their production.

The left auricle has a peculiar anatomical position, in that it is the posterior and superior chamber of the heart, thereby being in closest relation to the esophagus and to the bifurcation of the trachea. By virtue of this position the left auricle may enlarge to the right as well as to the left and during the course of its enlargement may exert pressure on the esophagus and main bronchi. There are many reports in the literature illustrating these effects, the least known of which is the last. Compression and displacement of the bronchi but rarely give rise to lung changes, yet may be frequently found by x-ray, and together with displacement of the esophagus are usually attributable to the left auricular enlargement. Roentgenological methods demonstrating the occurrence of these three phenomena are described which make more accurate the diagnosis of enlargement of the left auricle. 1. 1. Observation of right border of the heart for double curve in anteroposterior films and fluoroscopy to verify that the upper curve is identical with the posterior superior curve of the heart, and to note asynchronous pulsations of the two curves. This last makes the diagnosis of left auricular enlargement quite definite. 2. 2. Observation of displacement of the esophagus. The esophagus is displaced posteriorly and to the right by left auricular enlargement. 3. 3. Demonstration of bronchial displacement, particularly as noted in the films made in the left oblique position—in obese patients, after an injection of lipiodol. Bronchial compression and displacement in left auricular enlargement occur frequently and can be demonstrated by x-ray study: (a) by left oblique views; (b) in anteroposterior views following lipiodol injection.

D IFFICULTIES in the control of the hypothrombinemic effect of dicumarol@ in the treatment of thromboembolic diseases have led to the investigation of other coumarin derivatives. With one of these, tromexan@)t (3,3’-carboxymethylenbis [4-hydroxycoumarin] ethyl ester), the therapeutic effects take place more rapidly after administration of the drug and disappear more rapidly after discontinuance of the drug than is the case with dicumarol. These characteristics of tromexan are potential advantages in that they might be expected to permit more predictable control of induced hypoprothrombinemia. There was some confirmation of the early expectations1-5 but this has not been borne out in later studies.6*7 Previous works indicates that tromexan is rapidly and completely absorbed from the gastrointestinal tract, compared to the slow and sometimes incomplete absorption of dicumarol. Its biotransformation is rapid, the plasma concentration falling at an average rate of 25 per cent per hour, compared to dicumarol which falls at an average rate of about 40 per cent per day.g As with dicumarol the rate of metabolic transformation of tromexan varies widely in different subjects. The rapid disappearance of tromexan from the body is accompanied with a rapid return of the prothrombin time to pretreatment levels on discontinuing therapy. After a single dose the drug has almost disappeared from the body before the prothrombin response becomes evident, eight to twelve hours after drug administration.1 Single daily doses of the drug

SummaryClamping the aorta above the orifices of the renal artery in dogs is followed by elevation of the diastolic level of arterial pressure in the hind legs as well as in the carotid arteries. Constriction of the peripheral arterioles is, therefore, a general phenomenon, just as when it follows partial clamping of the renal arteries. The hypertension which develops in coarctation of the aorta in man is on this evidence analogous to that which accompanies constriction of the renal arteries. The evidence suggests strongly that interference with the hemodynamics of the renal circulation leads to hypertension in man as well as in animals.

Dynamic equilibrium in a biological system implies that the compartment under study does not change in size during the period of observation. In many biological systems there are, however, net changes with time and this report deals with the mathematical treatment necessary to calculate unequal rates of inflow and outflow. A method is presented for the calculation of transfer rates in a two compartment system when the rates of flow between these compartments are unequal but constant. Equations were developed to calculate the amount of material transported per unit time derived from measurements of specific activity and compartment size. The problems of (1) sampling from the pool and (2) the effects of analytical errors on the estimation of rate have been evaluated. An example has been presented in which the derived equations have been applied to a study of the simultaneous passage of sodium into and out of a permanently isolated loop of bowel.

1. Studies have been made of the behavior of renal blood flow after partial constriction of the renal artery in twenty-four dogs. 2. When reduction in renal blood flow is produced by partial constriction of the renal artery, a readjustment of flow in the direction of normal occurs within a few minutes, subsequent constriction being again followed by a return of flow toward normal until the artery is markedly constricted. 3. Renal blood flow after marked constriction of the artery becomes extremely susceptible to the vasoconstrictive action of small doses of adrenalin, and flow may cease with larger doses for a considerable period of time. 4. Arterial hypertension of significant degree may follow partial constriction of one renal artery during brief experiments when adrenalin in addition has been administered. 5. Further evidence is presented in favor of the concept that the renal circulation enjoys a control independent of systemic arterial pressure.

The phenomenon of fibrinolysis in thromboembolic disease is of great importance. In this communication the authors present striking evidence of fibrinolysis induced by drugs.

Vascular responses to warming were studied in hemiplegic patients and after sympathectomy, using venous occlusion plethysmography of foot and leg. Comparisons were made with corresponding age groups. The pattern of response was essentially unchanged in hemiplegic patients, but was altered substantially where sympathetic pathways had been interrupted.

1. 1. A method of obtaining continuous records of temperature is described in which the movements of beams of light reflected from the mirrors of galvanometers connected to thermocouples are photographed. 2. 2. relatively mild obstruction to the circulation of the extremities obtained by use of pressure cuffs about the arms and legs is followed promptly by rise in rectal temperature. 3. 3. In a warm environment, the rise of rectal temperature tends to be greater and the fall of surface temperature less than in a cool environment. 4. 4. The results suggest that the relatively mild and short obstruction to peripheral circulation used in these observations brings about elevation of rectal temperature and is consistent with the belief that elevation of rectal temperature encountered in the course of heart failure may be due simply to slowing of the peripheral circulation.

ConclusionsIn a group fo 19 elderly individuals with gray hair, a significant color change was noted during a period of intensive vitamin therapy in only 2 individuals; these subjects received both calcium pantothenate and para-aminobenzoic acid, together with brewer's yeast. Both were men. The fact that the only 2 substantiated results occurred in the group receiving both calcium pantothenate and para-aminobenzoic acid may be of importance. Some questionable changes were noted when one or the other drug was given alone.

Blood flow to the extremities and kidneys was measured simultaneously in normal subjects, hypertensive patients and patients with obliterative arterial disease of the lower extremities. The latter group showed diminished basal flow in the lower extremities, increased basal flow in the upper extremities, and a delayed and diminished response to reflex heating, compared with the normal and hypertensive subjects. In all three groups, the increase in extremity blood flow was regularly accompanied by a concomitant decrease in renal blood flow. No significant change in arterial pressure was observed.

Comparison of hemodynamic changes (cardiac output, renal plasma flow, and extremity blood flow) observed during reserpine-induced hypotension with those occurring during pentolinium-induced hypotension suggests better adaptation following reserpine. This difference is believed to be related to the gradation of onset of hypotension. It was found that reserpine-induced hypotension is potentiated by norepinephrine, and pentolinium-induced hypotension by serotonin. Pretreatment with the hypotensive agent increased the pressor response to norepinephrine and serotonin respectively, if the pressor substance was administered before the onset of hypotension.

1.1. Phenylbutazone exhibits antirheumatic effects in rheumatoid arthritis which are comparable to those shown by cortisone and corticotropin. 2.2. Like cortisone and corticotropin the drug causes urinary retention of sodium, chloride and water, and may reactivate peptic ulcers; but unlike cortisone it does not affect the excretion of potassium nor does it cause eosinopenia or increased ketosteroid excretion. It is concluded that the action of phenylbutazone is not mediated, directly or indirectly, through the adrenal cortex. 3.3. During phenylbutazone therapy there is often a fall in red cell count, hemoglobin and hematocrit which is primarily the result of hemodilution and not of depression of the hematopoietic system. 4.4. Plasma levels of phenylbutazone approach a limiting concentration as dosage is increased. This limiting concentration varies widely from patient to patient. Most subjects achieve plasma levels on 400 to 600 mg. daily that are only slightly lower than when 800 mg. are given.

The simultaneous unidirectional flow of sodium into and out of isolated loops of jejunum, ileum and colon of the dog, has been measured, in vivo . Four loops of bowel observed over a 5-year period did not degenerate physiologically or histologically. The variability of sodium flux, measured repeatedly over the five years, was no greater in experiments conducted 1 day apart than in those conducted over a period of years. Adrenalectomy did not reduce this inherent variability. Moderate salt loading by intravenous administration, or by dietary intake, did not alter the transfer rates of sodium across the intestine. Approximately 1 ml of water was transferred into and out of a 20-cm length of intestine/min. Sodium concentration was usually maintained at 144 mEq/l. in the lumen of the small intestine, while sodium concentration in the lumen of the large intestine usually decreased to be partially replaced by potassium. It is suggested that the rates of sodium flow across the dog intestine, in vivo , are of the same order of magnitude per unit surface area as those of sodium flux across amphibian tissues, in vitro . While water may enter the amphibian tissue 50 times as fast as sodium, water and sodium traverse the dog intestine in the ratio of their free diffusion coefficients, water moving twice as fast as sodium.

Adrenergic blocking with Dibenzyline measurably enhances the healing of ischemic ulcers. Eleven cases of obliterative arterial disease and two cases of Raynaud's disease were closely observed and are reported in detail. In six of the individuals suffering from obliterative arterial disease, changes in blood flow were documented by plethysmography. Dibenzyline measurably influenced intermittent claudication only after prolonged administration (three to four months) in four out of eight closely observed patients without ulcers. The results of the physiologic tests suggest that during the early phases of adrenergic blocking the increase in blood flow is mostly in the skin, while in the later phases increase in blood flow through the muscle predominates.

Surface temperature response to 15 agents was studied at 20 C. and 55 per cent humidity. Toe temperature was considered representative of the body's "glomus area." Temperatures at forehead and cheek represented the "blush area." Diethylaminoethanol, Hydergine, tetraethylammonium chloride, Priscoline, hexamethonium, Ilidar and Dibenzyline produced a prompt rise in temperature in the glomus area without affecting the temperature in the blush area; nicotinic acid, Roniacol, histamine and papaverine caused the opposite response. Nitroglycerin had no effect on the temperature in the blush area; with the subject recumbent, it caused a fall in the glomus area. Hypertonic saline, aminophylline and Banthine had no effect on either glomus or blush areas.

Ten healthy volunteers (five males and five females), 25 to 41 years of age, were exposed to several different environmental conditions in a constant temperature room. It was found that at 20 C. and about 55 per cent humidity, about five hours after the last meal, the behavior of the temperature of the toe in contrast to that of the finger was consistent, reliable and reproducible. These conditions, somewhat cooler than those frequently used, were deemed suitable for testing vasodilator drugs or procedures.

A Dibenamine analogue was administered orally to five hypertensive and 10 normotensive subjects over periods from 14 to 21 days. Its adrenergic blocking effect was studied by observing blood pressure, pulse rate, skin temperature of the toes and the pupillary mechanism. Nasal congestion, weakness, listlessness, dizziness, drowsiness and palpitation were persistent sequelae of adrenergic blocking. The drug was found valuable for investigation of autonomous nervous system functions and may hold promise as a therapeutic agent for the treatment of arterial insufficiency and some types of hypertensive subjects.

Excerpt INTRODUCTION There has been considerable interest for many years in vasomotor responses to nicotine and to the smoking (or chewing) of tobacco. There is almost complete agreement that smoki...

SummaryAbnormalities of the urinary tract, as demonstrated in pyelograms obtained after intravenous injection of diodrast are frequently present in young persons suffering from “essential hypertension.” In 50 of 71 patients some abnormality was present. Under these circumstances it seems desirable to explore further the meaning of these phenomena.