Magnetic determination of the relationship between the S-T segment shift and the injury current produced by coronary artery occlusion. Both the S-T segment shift and the injury current were measured using the direct-current magnetocardiogram (d-c MCG) in seven dogs undergoing coronary artery occlusion. The purpose of the measurements was to clarify the origin of the S-T shift in acute ischemia and infarction. Previous measurements, consisting of d-c electrograms recorded from the exposed epicardial surface in situ, are partially inconsistent; also, they are not necessarily representative of the surface electrocardiogram (ECG), which sums broadly over the myocardium. The d-c MCG allows steady myocardial currents in the intact torso to the measured externally; because the d-c MCG sums broadly over these currents, conclusions drawn from it are applicable to the ECG. Coronary artery occlusion was produced by inflating a tube which, about 1 week earlier, had been surgically installed around the artery and exteriorized. During occlusions carried out in the MIT magnetically shielded room, a sensitive magnetometer recorded the d-c MCG at various locations around the torso. Within 20 seconds after occlusion, equal and opposite S-T segment and base-line (d-c) shifts appeared on the d-c MCG; these shifts were maintained for at least 15 minutes, after which they slowly decreased. Therefore, during the acute ischemia produced by these occlusions, the S-T shift is a secondary result of a primary injury current that is interrupted during the S-T interval.


Dynamics of glomerular ultrafiltration in the rat. VIII. Effects of hematocrit. This study was undertaken in an effort to examine the effects of selective variations in systemic hematocrit on the preglomerular, glomerular, and postglomerular micocirculation in the rat. By isovolemic exchange transfusions, systemic hematocrit (control 51 ml/100 ml) was either reduced (21 ml/100 ml, N equal 7 rats) or elevated (62 ml/100 ml, N equal 7). Single nephron glomerular filtration rate varied inversely and filtration fraction varied directly with the changes in hematocrit. The fall in filtration fraction with decreased hematocrit was due to a decline in the measured glomerular transcapillary hydraulic pressure difference and to a marked increased in the initial glomerular plasma flow rate. Afferent (RA)and efferent (RE) arteriolar resistance declined with the fall in hematocrit; RA fell proportionately more than did RE. The rise in filtration fraction with the elevation in hematocrit was due to a marked increase in  in part due to a relatively greater rise in RE than in RA. These findings provide an attractive explanation for the general tendency for filtration fraction to vary directly with hematocrit in anemic and polycythemic states in man.


Disorders of cellular electrophysiology produced by ischemia of the canine His bundle. In the first 4 hours after occlusion of the anterior septal coronary artery, 18 dogs developed bundle branch block, heart block, or both. The hearts were then excised, and preparations were dissected to expose the His bundle and the bundle branches, which were superfused with modified Tyrode's solution at 37 degrees C. In the His bundle and the most proximal bundle branches, resting potentials were reduced and diminutive action potentials had slow upstrokes, often with notches or steps. Action potentials were generated by fibers that had resting potentials between--40 and --50 mv. Conduction was impaired; conduction velocities less than 0.01 m/sec were sometimes observed. In more severely affected cells, refractoriness outlasted repolarization. Encroachment on the prolonged refractory period resulted in further diminution of action potentials and continuous rather than intermittent block. More commonly, the response to rapid rate took the form of intermittent block with progressive conduction delay in the series of conducted beats, culminating in a blocked beat (Wenckebach sequence). There was a fatigue factor that accumulated at short cycle lengths and depressed the action potential. Automaticity was not enhanced, but pacemaker function was abnormal. The threshold potential shifted erratically, and pacemaker potentials sometimes were intermittently diminished, resulting in intermittent failure to propagate. During prolonged superfusion, there was a tendency to recover with a drift of the maximum diastolic potentials toward more negative levels. None of these changes were found in ten hearts excised from dogs in which the coronary artery had not been ligated.


Hemodynamic and humoral characteristics of hypertension induced by prolonged stellate ganglion stimulation in conscious dogs. Recent evidence has suggested that cardiac factors may play a role in the evolution of arterial hypertension. To test the possibility that an increase in cardiac-performance can lead to a sustained increase in systemic blood pressure, we electrically stimulated the left stellate ganglion of six conscious dogs continuously for a 7-day period and monitored cardiac output and arterial blood pressure. In all six dogs, stimulation elicited an abrupt rise in systemic blood pre-sure that was entirely due to rise in cardiac output that lasted at least 6 hours. After 1 day of continuous stimulation, cardiac output retured to control values, but blood pressure remained elevated. After 7 days of stimulation, blood pressure was increased by an average of 25 mm Hg and peripheral resistance by 35 plus and minus 4%. Measurements of blood volume, plasma renin activity, circulating catecholamines (three of the six dogs), and sodium balance showed that none of these factors could explain the development pf this sustained hypertension. Pharmacologic blockade with phenoxybenzamine prevented in large part the rise in blood pressure in short-term stellate ganglion stimulations, whereas propranolol had very little effect on the pressor response, although it nearly abolished the increase in cardiac output. The data indicate that continuous stimulation of the stellate ganglion in conscious dogs leads to substained rises in both blood pressure and peripheral resistance; these changes are apparently mediated by increased activity of the sympathetic nervous system.


Thickenings in the coronary arteries in infancy as an indication of genetic factors in coronary heart disease. In Finland, mortality from coronary heart disease is high, and much higher in the eastern than in the western countries. Both left and right coronary arteries of 141 children who died under one year of age at the Children's Hospital, University of Helsinki, were investigated. Thirty-two of these children formed a western and 41 an eastern group according to the birthplaces of their grandparents in Finland. Correlations were tested between this geographical distribution and some dimensions of the coronary arteries, as well as other clinical variables. The inner vascular layers of the left coronary arteries were found to be thicker in the eastern group (P less than 0.05 in analysis of variance and P less than 0.01 in regression analysis). No other significant correlations were observed. This association of infants having thick inner vascular layers in the coronary artery with a population group where mortality from coronary heart disease (CHD) is very high supports the hypothesis that the thickenings are prearteriosclerotic. The difference found between the arteries of the western and eastern groups might be due to a difference in the vulnerability of the inner vascular wall to extrinsic deleterious factors. The association substantiates the existence of a genetic component in the etiology of CHD and supports the theory that two separate groups of settlers originally colonized Finland.


Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Electrophysiological studies in five patients with documented (4) or suspected (1) paroxysmal supraventricular tachycardia (PSVT), suggested sinus or atrial reentrance (SR or AR). Two of the patients had preexcitation, three had evidence of atrial enlargement, and all had organic heart disease. The following observations supported a diagnosis of SR and AR; 1) induction of sustained PSVT with atrial extrastimulus technique allowing definition of an echo zone; 2) induction of sustained PSVT during constant rapid atrial pacing at a rate less than that producing A-V nodal Wenckebach periods, or producing normalization of QRS complex in patients with pre-excitation: 3) P waves preceding each QRS during PSVT with an A-H interval appropriate for the rate of the PSVT; 4) antegrade P wave morphology during PSVT, a normal high to low sequence of right atrial activation (SR), or P wave morphology and atrial activation sequence different from sinus (AR); 5) lack of correlation of PSVT induction with critical A-H interval. The rates of induced sustained PSVT ranged from 114 to 143 beats/min, and were similar to those observed during spontaneous episodes of PSVT in the four patients. PSVT could be terminated with critically timed extra-stimuli or carotid massage. In conclusion, SR and AR appear to be mechanisms of spontaneous PSVT in man. Rates of SR and AR PSVT tend to be relatively slow.


Eectrophysiological observations in pateints with rate dependent bundle branch block. Electrophysiological studies were conducted in 15 patients with tachycardic rate dependent bundle branch block (RDBBB): ten with left, and five with right. No bradycardic RDBBB was observed, despite occurrence of cycle lengths (CL) longer than 1200 msec in over half the patients studied. Onset of RDBBB was abrupt in 13 patients, and gradual in two. In three patients, the CL allowing reversion to normal conduction (once RDBBB was initiated) was 50, 55, and 190 msec longer, respectively, than the CL inducing RDBBB. Bundle brance refractory periods (RP) were measured with atrial extrastimulus technique in five patients. All RP (except one) were prolonged at all tested CL when compared to patients without conduction disease. The expected decrease in RP with shortening of CL did not occur in four of the five patients. The electrophysiological abnormality in patients with DBBB thus appeared to be an increase in refractoriness in the affected bundle branch, along with a loss of the normal decrease in refractoriness with decrease in CL. Similar findings might be demonstrable in patients with early bundle branch disease.


Mitral commisurotomy versus replacement. Preoperative evaluation by echocardiography. Echocardiographic studies of the mitral valve were performed in 57 patients with pure or predominant mitral stenosis who subsequently underwent surgery (30 commissurotomy, 27 valve replacement). Mitral valve calcification was graded heavy (thick, conglomerate echoes), light (multiple, discrete linear echoes) or none (thin, single or duplicate signals). Valve mobility, measured as the excursion from the systolic closed position to the fully opened position in diastole, was classified as normal (20 mm or over), restricted (16-19 mm) or poor (15 mm or less). Absence of mitral valve caclification was the most useful echocardiographic indicator for commissurotomy (18 of )9 cases. The most reliable criteria for valve replacement were heavy valve calcification (11 of 11 cases) and poor cusp mobility (11 of 11 cases). The poor mobility group included 3 patients with heavily calcified valves. Thus 37 of 57 cases (65%) could be reliably categorized regarding the type of surgery performed using these three parameters. The remaining echocardiographic parameters (normal mobility, restricted mobility and light calcification) were less valuable in the assignment of the operative category. Echocardiographic assessment of mitral valve calcification and mobility appears to be of value in planning the surgical approach in patients with pure or predominant mitral stenosis.


Echocardiography of the tricuspid valve in congenital left ventricular-riht atrial communication. Two patients, ages 14 and 18, with congenital left ventricular-right atrial communication through a defect in the tricuspid valve were studied by echocardiography. Proof was obtained by angiocardiography and surgery in one and ultrasonic contrast injection and angiocardiography in the other. Both presented clinically as uncomplicated ventricular septal defects. Echocardiography consistently demonstrated a high frequency, low amplitude flutter of the tricuspid valve in systole and none in diastole. Following surgical correction of the defect in one patient, there was complete disappearance of the systolic flutter. Systolic flutter has not been observed with tricuspid incompetence nor with other forms of ventricular septal defects. Fistulous communication from the aorta to the right atrium just above the tricuspid valve did not demonstrate systolic flutter in one patient studies. Tricuspid valve systolic flutter appears to be caused by the passage of the left ventricular jet blood into the right atrium through a defect in the tricuspid valve. Echocardiographic study of the tricuspid valve is of value in the recognition of the congenital left ventricular-right atrial communication.


Echographic assessment of atrial transport, mitral movement, and ventricular performance following electroversion of supraventricular arrhythmias. Controversy attends the extent and temporal sequence of improvements in hemodynamic function resulting from the return of atrial contraction following cardioversion of supraventricular arrhythmias. Thus, mitral, left atrial (LA) and left ventricular (LV) echograms were obtained before and one hour after conversion of supraventricular arrhythmias to normal sinus rhythm by direct current countershock in patients with chronic coronary disease or cardiomyopathies without valvular dysfunction. The duration of the rhythm disturbance varied from one day to five years in 22 patients and was indeterminate in 13. Atrial systole immediately produced prominent mitral "A" waves with anterior valve excursion of 7.5 mm (range 3 to 12) in 33 of the 35 patients (94%). The two patients with atrial electromechanical dissociation reverted to atrial fibrillation within one week. Cardioversion caused a decline in LA diameter (3.5 to 3.2 cm, P less than .001) and a rise in LV end-diastolic dimension (5.2 to 5.5 cm, P less than .001) while LV end-systolic dimension was unchanged (4.2 cm). Thereby stroke volume rose. Heart rate fell an average of 16 beats/min. Depressed cardiac output was improved + 0.84 L/min/m-2. Thus, in the majority of patients with acute or chronic supraventricular arrhythmias without mitral valve disease, cardioversion promptly restores effective atrial contraction, decreases LA size, and results in substantial hemodynamic benefit.


Echocardiographic observations on the mechanism of production of the second heart sound. This investigation was designed to determine the echocardiographic correlates of the aortic and pulmonary components of the second heart sound. Simultaneous recordings of the ECG, phonocardiogram, carotid pulse tracing and the echocardiogram of the aortic valve were made in 54 patients. The tracings were recorded at a paper speed of 100 mm/sec, with 20 msec time lines. Aortic valve closure (AVC) on the echocardiogram occurred before the onset of the aortic component of the second heart sound (A2) in all but two patients. The mean AVC-to-A2 interval was 12 msec with a range of 5 to 25 msec. Simultaneous recordings of the pulmonary valve echocardiogram, ECG, phonocardiogram and carotid pulse tracing were made in 14 patients. Pulmonary valve closure (PVC) on the echocardiogram preceded the pulmonary component of the second sound (P2) in all patients. The mean PVC-2 interval was 60 msec with a range of 30 to 75 msec. We conclude that aortic valve closure and pulmonary valve closure are not directly responsible for the genesis of the second heart sound (S2). These observations are consonant with the theory that S2 is caused by deceleration of columns of blood resulting from semilunar valve closure, throwing the cardiohemic system into vibration.


Echographic determination of left ventricular volumes in pediatric patients. The purpose of this study was to validate the accuracy of determining left ventricular (LV) volumes by echocardiography in infants and children. Thirty-one patients between the ages of two months and 15 years underwent left ventriculography (biplane antero-posterior and lateral cine). Ventricular volumes using an ellipsoidal model were calculated for end diastole from the cineangiograms. There was a strong correlation (r = 0.856) between the echographic minor dimension (Be) and the minor lateral cine dimension (Bc) at end diastole. A similar correlation (r = 0.889) existed between the LV volume in end diastole measured by cineangiography and Be. The correlation coefficient between the echo minor dimension and the lateral minor cine dimension in end systole was 0.753. A relation between ejection fraction (EF) and the echo minor dimension measurements in end diastole and end systole was formulated, which permitted estimation of the EF from the echo measurements. As a result of this study, it was concluded that the LV minor dimension can be measured reliably by echocardiography in children and from these measurements LV volumes, ejection fraction, and hence, stroke volume can be estimated.


Measurement of right and left ventricular systolic time intervals by echocardiography. One of the noninvasive methods of evaluating left ventricular performance is the measurement of left ventricular systolic time intervals (LVSTI). However, noninvasive measurement of right ventricular systole by this technique has been unreliable because of the inability to accurately time the onset of right ventricular ejection. Excellent correlation of LVSTI measured from the carotid pulse and those determined from the echocardiogram was demonstrated in 15 patients. STI of the right ventricle (RVSTI) were measured in a similar fashion from the pulmonary valve echo in 11 normal children. Right ventricular ejection time (RVET) was longer than left ventricular injection time (LVET). Right ventricular pre-ejection period and RPEP was shorter than left ventricular pre-ejection period (LPEP). In 15 children with transposition of the great arteries (TGA) the situation was reversed. RVET was shortened and RPEP was prolonged as the right ventricle contracted against systemic resistance; whereas, the LVET lengthened and LPEP shortened with ejection into a low pressure pulmonary circuit. Our studies in a total of 41 patients indicate the accurate, noninvasive measurement of right, as well as left, ventricular STI can be obtained with the use of echocardiography.


A comparison of systolic time intervals derived from the central aortic pressure and from the external carotid pulse tracing. In 26 patients a direct comparison was made of systolic time intervals derived from the right and left external carotid pulse tracing and from the central aortic pressure, simultaneously recorded by means of a catheter-tip micromanometer. In addition, the delay time (required for pulse wave transmission to the neck) of the upstroke (DUEC) and incisura (DIEC) of the external carotid pulse tracing was studied. The influence of changes in heart rate on these intervals was evaluated by right atrial pacing. At resting frequencies DUEC exceeded DIEC by 4 to 4.5 msec (P less than 0.005). Increasing heart rate did not influence DUEC but prolonged DIEC. Differences between DUEC and DIEC were associated with a decrease and reversal with increasing heart rate (tau = 0.52, on the right carotid pulse; tau = 0.65, on the left pulse). Internally and externally measured left ventricular ejection time and pre-jection period were strongly correleated. Significant differences in absolute values were also observed. Whether these differences were positive or negative was dependent on heart rate. At rest external left ventricular ejection time was 4 to 4.5 msec (P less than 0.005) shorter, external pre-ejection period 5.5 to 6 msec (P less than 0.005) longer than corresponding intervals measured internally. At heart rates above plus or minus 100 beats/min the relationships were reversed. No significant differences could be demonstrated between these intervals measured on the right and left external carotid pulse.


The apical A wave versus the fourth heart sound in assessing the severity of aortic stenosis. The height of the "a" wave of the apexcardiogram was evaluated as a marker for critical aortic stenosis in patients over 40. Critical aoritc stenosis was defined as an aortic valve area less than .75 cm-2 with no more than mild aortic insufficiency. Phonocardiograms and apexcardiograms were performed on 72 patients with catheterization proven aortic stenosis and on 14 normal controls, all over age 40. The height of the "a" wave of the apexcardiogram was measured as a percentage of the e to o excursion (a/e-o). Fourth heart sound gallops ( S4G) were recorded in 71% (11 of 14) of normal controls, 86% (6 of 7) of patients with less than critical aortic stenosis, and 85% ( 55 of 65) of patients with critical aortic stenosis. The a/e-o was less than 16% in all normals or patients with less than critical aortic stenosis. The a/e-o exceeded 16% in 45% (29 of 65) with critical aortic stenosis. Audibility of the S4G bore no relationship to recordability, apical "a" wave geight, or the severity of the aortic stenosis. In conclusion, therefore, we believe that when one is confronted with findings suggestive of aortic stenosis, the finding of a palpable apical "a" wave (or an "a" wave height of greater than 16% of the total complex on the apexcardiogram) is an important positive feature, suggesting severe aortic stenosis. Its absence, however, does not exclude severe valvar obstruction. Probably because of auscultatory inaccuracy in this condition, the apparent presence or absence of an S4G has not been of much aid in this evaluation. This sound, however, might be more useful in a carefully performed prospective study.


Clinical use of sodium nitroprusside in chronic ischemic heart  disease.  Effects on peripheral vascular resistance and venous tone and on ventricular volume, pump and mechanical performance. Although hemodynamic benefit has been shown with sodium nitroprusside (NP) in acute coronary pump failure, complete understanding of the mechanisms of action of the agent on the cardiocirculation and its value in chronic ventricular dysfunction are lacking. This investigation evaluates the effects of NP on the systemic and regional arterial and venous beds and on cardiac dynamics, ventricular volumes, contractile state and myocardial energetics in long-standing congestive heart failure. Twelve patients with chronic coronary pump dysfunction received NP infusion to lower systolic pressure to 95-105 mm Hg. Left ventricular (LV) function was assessed directly by angiographic volumes and high fidelity pressure, and peripheral circulatory dynamics were determined simultaneously by forearm arterial and venous plethysmography. NP reduced mean arterial pressure (MAP) from 88.2 to 73.4 mm Hg (P less than 0.05) and significantly (P less than 0.05) enhanced the variables of LV performance: LV end-diastolic pressure (EDP) diminished from 18.5 to 9.9 mm Hg; ejection fraction rose from 0.47 to 0.55; percent of LV segmental shortening increased; and isovolumic and ejection indices of contractility improved. Concomitantly, NP reduced the indices of myocardial oxygen demands of ventricular tension time index and LVED volume index. These salutary effects on LV performance and energetics occurred secondary to peripheral arterial and venous dilation (P less than 0.05) produced by NP: total systemic vascular resistance was lowered from 1590 to 1310 dynes sec cm--5; forearm vascular resistance diminished from 46 to 37 mm Hg/ml/100 gm/min; and forearm venous tone fell from 14.2 to 10.1 mm Hg/cc. Depressed stroke index (SI) and cardiac index (CI) increased (P less than 0.05) with NP: despite the fall in LVEDP, when ventricular filling pressures with the agent were at levels slightly above normal. Dextran infusion given with NP to restore LVEDP to moderately elevated values increased SI and CI (P less than 0.05) when NP alone produced no change in stroke output. Thus, the peripheral vasodilator properties of nitroprusside improve LV function by reducing impedance to ventricular ejection, while MVO2 is diminished by decreasing LV preload and afterload through relaxing actions


Transfemoral plug closure of patent ductus arteriosus. Experiences in 61 consecutive cases treated without thoracotomy. We successfully closed the isolated patent ductus arteriosus in 58 of 61 consecutive patients using the transfemoral-catheter method originally introduced by Porstmann in 1968. To perform this technique more safely and reliably, some instrumental and technical improvements were made. The indications for this method have been expanded to include the cylindrical or window-type ductus as well as the conical-shaped ductus. Classification into three groups of the configuration of the ductus by angiography has been useful in selecting the shape of the closing plug. Whenever feasible, we consider the catheter technique to be the method of choice to close the ductus.


Hemodynamic features of prolapsing and nonprolapsing left atrial myxoma. In the course of the evaluation of five patients with left atrial myxoma, it was noted that the movement of the myxoma was related to specific changes in left atrial hemodynamics. Prolapsing tumors, Type I, move from the left ventricle to the left atrium in early systole and from the left atrium to the left ventricle in early diastole, thereby causing prominent c and v waves accompanied by a rapid y descent. Nonprolapsing tumors, Type II, remain in the left atrium during the entire cardiac cycle, impeding flow across the mitral valve. In these latter cases, the y descent is slow and indistinguishable from that caused by mitral valvular stenosis. The cineangiocardiograms and echocardiograms corroborate these two types of hemodynamic observations. The particular value of direct echocardiographic examination of the left atrium prior to cardiac catheterization was evident in two of the three patients with nonprolapsing tumors. Since the hemodynamic pattern of nonprolapsing left atrial myxoma resembles that of mitral valvular stenosis, it is stressed that echocardiography should have an important place in precatheterization assessment of patients with mitral valve disease. If left atrial myxoma is suspected clinically or on the basis of echocardiographic findings, regardless of the pressure curve contours, transseptal cardiac catheterization should be avoided and the left atrium visualized by pulmonary angiography levophase.


Platelet survival time following aortic valve replacement. Thromboembolism continues to complicate the course of patients following aortic valve replacement. In patients with prosthetic and homograft mitral valves, platelet survival time has been shown to correlate with occurrence of thromboembolism. This study extends these observations to patients with aortic valve disease. Platelet survival time was measured (by the chromium-51 method) in 73 patients with aortic valve disease. Eighteen patients were studied preoperatively and had platelet survival times of 3.4 plus or minus 0.14 days (mean plus or minus standard error of the mean), almost the same as normal (3.7 plus or minus 0.4 days). Platelet survival time was shortened (P less than 0.001) following aortic valve replacement with Starr-Edwards prosthesis - Model 1000: 2.5 plus or minus 0.13 days (N = 6); Model 1200-1260: 3.0 plus or minus 0.10 (n = 14); model 2300-2320: 3.0 plus or minus 0.15 days (N = 9) - and with stented aortic homografts: 3.0 plus or minus 0.10 days (N = 16). Platelet survival time was normal following aortic valve replacement in patients with directly sewn aortic homografts 3.7 dats plus or minus 0.24 days (N = 10). Eleven patients with Starr-Edwards prostheses had a history of thromboembolism and all also showed shortened platelet survival time (2.7 plus or minus 0.12 days, P less than 0.001), a measurement which was significantly different (P less than 0.01) from the 18 patients with Starr-Edwards prostheses and no thromboembolism (3.0 plus or minus 0.09 days). Platelet suppressant therapy prolonged platelet survival in eight patients with Starr-Edwards devices, thromboembolism, and shortened platelet survival time. These results suggest that insertion of Starr-Edwards valves and stented aortic homografts alter platelet survival time but that direct homografts do not. A correlation between occurrence of thromboembolism after aortic valve replacement and shortened platelet survival time has been shown.


Predictive implications of stress testing. Follow-up of 2700 subjects after maximum treadmill stress testing. Follow-up data on 2700 subjects who had had maximum stress tests were assembled in life tables. A positive test, characterized by ST-segment depression of 1.5 mm, 0.08 sec from the J point, predicted an incidence of some new coronary event of 9.5% a year, as compared with 1.7% in those with a negative test. The incidence of infarction and death was also significantly higher than in the negative responders. Early onset of ischemia occurring at moderate exercise (4 metabolic equivalents-METS) resulted in an incidence of all coronary events of 15% a year, while ischemia first manifested at the seventh minute of exercise (approximately 8 METS) results in an incidence of only 4% per year. The magnitude of ST depression and the age of onset of ischemia failed to influence the incidence of coronary events. A myocardial infarction previous to the test increased the incidence of events in both positive and negative responders. The positives with a previous infarction had more than double the incidence of coronary events than the positive responders with no pre-existing infarction. Those with chronotropic incompetence had a high incidence of coronary events even though the ECG response to exercise was normal.


Learned control of blood pressure in patients with high blood pressure. Five patients with documented histories of essential hypertension of at least ten years' duration participated in a triphasic study of training to control systolic blood pressure (SBP). Phase 1 was a seven week period during which patients took their BP (systolic and diastolic) at home and mailed these data to us daily. Phase 2 was a three week period during which patients were taught to control SBP using a noninvasive technique: patients were trained to raise, to lower and to alternately lower and raise SBP. Phase 3 was a three month period during which patients again took their BP at home and mailed these data to us daily. (1) all patients learned SBP control: average increas  15%; average decrease  11%; (2) during SBP control heart rates, breathing rates, triceps brachii muscle tension and EEG activity did not change; (3) follow-up tests at one and three months showed evidence of retained SBP control; (4) baseline SBP fell from 153 mm Hg during laboratory training to 135 mm Hg at the three month follow-up; (5) phase 3 home BPs fell 18/8 mm Hg from phase 1 levels; (6) at home patients also were able to reduce SBP from 141 mm Hg (average) to 125 mm Hg (average) by means of the lowering technique learned in the laboratory.


De subitaneis mortibus.  X. Familial congential heart block. Complete heart block was found shortly after birth in a brother and sister (not twins). Both were treated by electronic pacing because of symptoms attributable to inadequate cardiac output and electrical instability of heart. The boy has done well with his artificial pacemaker and is now six years old. His sister died of complications due in part to the large size of her pacemaker and small size of her body. At necropsy special studies of her heart included the centers for normal impulse formation and concuction. The primary abnormalities were at the junction of atrial septum with atrioventricular (A-V) node, and at the origin of the two bundle branches from the His bundle. The A-V node was isolated by collagen at all its margins except its junction with the His bundle. The proximal His bundle was essentially normal, but from that point on through the initial protions of both the left and right bundle branches there was extensive caseous degeneration which interrupted any possible conduction. These findings are discussed in relation to fetal and postnatal development of the human A-V node, and the His bundle and its branches; and in the context of a recently observed mathematical relationship between sinus rate and two forms of experimentally produced A-V junctional escape rhythms.


The deceptive aortic root.

The deceptive aortic root. Coronal, horizontal, and sagittal sections through the mid-line are excellent ways of depicting the anatomical position of the aortic root and for studying its topographical relationship to the surrounding vascular structures. Minimal radiographic abnormalities or no abnormalities at all may be present with an enlarged ascending portion of the thoracic aorta. Thus, frontal chest roentgenograms obtained with high kilovoltage, fluoroscopy and left anterior oblique projections should be utilized routinely for the evaluation of the ascending aorta. Calcification of the aortic valve and of the coronary arteries and the study of aortic valve prosthesis also demand a dynamic study and the use of complementary views, such as lateral and both oblique projections.


Comparison of methods for calculating serum osmolality form chemical concentrations, and the prognostic value of such calculations. Sodium, potassium, glucose, blood urea nitrogen, and osmolality were determined for 715 hospital-patient sera. The chemical concentrations were used to calculate osmolalities according to 13 different methods taken from the literature. The goodness of the comparison between calculated and measured osmolality was quite similar for several of the better methods. The aggreement was unimproved when molal chemical concentrations were used instead of molar values. The difference between measured and calculated osmolality was unrelated to whether a patient was discharged from the hospital after a short or long period or ultimately died. The equation we found to yield the most accurately calculated osmolalities is Osmolality = 1.86 Na + (Glu/18) + - (BUN/2.8) + 9.


Immunochemical determination of serum albumin with a centrifugal analyzer. The turbidity resulting from the reaction between albumin and specific anti-human serum was measured with a good precision by using a GEMSAEC centrifugal analyzer. The reaction was enhanced by polyethylene glycol to shorten the reaction time (5 min) and to displace the point of equivalence between antigen and antibody to an albumin concentration unlikely to occur in human sera (about 100 g/liter). An additional program for the computer was necessary to fit the absorbance readings of individual sera to the nonlinear standard curve. Serum albumin values obtained by the described method correlated well with values obtained by the electro-immuno-technique. About 100 samples could be analyzed per hour, 500 mul of 100-fold diluted antiserum being used per specimen.


Routine radioimmunoassay of plasma testosterone, and results for various endocrine disorders. We describe a modification of published methods for radioimmunoassay of plasma testosterone. This simpler method involves no chromatographic steps, and the necessary reagents, including tritiated testosterone and testosterone anti-serum, are commercially available. A digital computer is used for the calculation. Without difficulty, a technician can complete 100 assays in three working days. Mean testosterone concentrations (plus or minus 2 SD) in the plasmas of 21 normal men and 26 women with a normal menstrual cycle were 684 plus or minus 300 and 45 plus or minus 20 ng/dl, respectively. Within- and between-assay precision (coefficient of variation) were 5.2% (n = 29) and 6.7% (n = 26), respectively. We have assayed more than 1000 samples during the past year. We give data on the concentrations of testosterone in plasma of patients with various endocrine disorders.


Effects on radioimmunoassay of digoxin of varying incubation periods for antigen---antibody reaction and varying periods of absorption by dextran-coated charcoal. In radioimmunoassay of digoxin by the dextran-coated charcoal method, duration of the incubation period for the antigen-antibody reaction and time allowed for dextran-coated charcoal to absorb the free antigen are critical factors. We compared effects of prolonged periods of absorption on results obtained with five commercial kits. In all cases, the digoxin concentrations increased linearly with absorption time, but the increase varied among kits. Kallestad and New England Nuclear 3h-kits and the Squibb 125I-kit showed less increase (i.e., gave relatively consistent results after various periods of absorption); the Schwarz/Mann 125i-kit and Clinical Assays 3h-kit showed greater increases. Precautionary steps are outlined for radioimmunoassays by this technique.


Theory of photometric errors applied to the design and evaluation of a high-performance filter photometer. We have applied a comprehensive theory of photometric errors to the design and evaluation of an inexpensive stabilized photometer. The photometer is described in terms of a group of modules, the characteristics of which are described in terms of their effect on specific error coefficients. Procedures described in this paper show how the principles described earlier [Clin, Chem. 20, 1028 (1974)] can be used to optimize the design of new instrumentation. Chemical data are included to verify the agreement between predicted and experimental results.


Presence of carotenoids in the erythrocyte membranes of carotenemic and noncarotenemic individuals. Erythrocytes and erythrocyte membranes obtained from carotenemic (serum carotene greater than 4.0 mg/liter) and noncarotenemic individuals contain a small amount of carotenoid pigments. The principal pigment isolated from erythrocytes and erythrocyte membranes from carotenemic individuals cochromatographed with, and has an absorption spectrum similar to, authentic beta-carotene. Traces of beta-carotene were also found in the extracts of the erythrocytes and membranes obtained from the noncarotenemic individuals. These pigments were demonstrable only when the erythrocytes were extracted in the presence of an anti-oxidant (pyrogallol). Anti-oxidants should be used in the extraction and saponification process when only small samples are available or when only small amounts of carotenoid pigments are present in the material to be extracted.


Lecithin---sphingomyelin ratio in amniotic fluid, as assessed by a modified thin-layer chromatographic method in which a commercial pre-coated plate is used. Commercially available pre-coated thin-layer chromatographic plates consisting of silica gel supported on aluminum sheets were used to determine the lecithin-sphingomyelin ration in samples of amniotic fluid. These lipids were separated in chloroform-methanol-water (65:25:4 by vol) solvent system (lecithin Rf = 0.33; sphingomyelin, Rf = 0.25), and the spots were made visible in 5-15 min by heating to 180 degrees C after spraying with a solution of copper acetate (30 g/liter) in aqueous phosphoric acid (80 g/liter). The lipids were measured densitometrically after "peeling off" the adsorbent containing the spots by using a transparent cellulose ("Scotch brand") adhesive tape. Virtues of the original Gluck procedure are retained without need to heat the plates to 280 degrees C after spraying with corrosive aqueous sulfuric acid (698 g/liter) to make the lipids visible. Results for synthetic mixtures in concentrations within the physiological range and with a ratio of 0.5 to 3.0 showed an accuracy of 99% pluss or minus 7% (SD.).


Evaluation of the Corning 940 Calcium Titator for use with serum and urine. The Corning 940 Titrator, which measures total calcium concentration by titration with [ethylenebis(oxyethylenenitrilo)]tetraacetic acid, was evaluated for use in hospital laboratory. Calcium values for patients' sera were about 0.3 mg/dl lower as measured with the Titrator than with the Technicon SMA 12/60 continuous-flow analyzer. A similar bias was evident when the results with the Titrator were compared with those from atomic absorption spectrophotometry. Agreement was better in the low range and worse in the high range. Within-day and between-day coefficients of variation on the Titrator were about 1.5% and 2.5%, respectively. We saw no interference from magnesium, phosphorus, bilirubin, or in the presence of lipemia. At extremely increased hemoglobin concentrations (500 mg/dl), there is a 5% inhibition. Titrator results for patients' urine samples correlated closely (n = 0.999) with those obtained with the SMA 12/60.


Some nonparametric statistical tests for quick evaluation of clinical data. Some rapid statistical tests give (a) rapid answers on how well methods agree and control chart evaluation (sign and run tests) and (b) evaluation of distribution of test results (Tukey's quick test and run test). These tests mainly require counting of data and the use of the given nomograms. An unusual distribution of patient test values--that is, unusual when compared with the generally observed distribution of the data seen in a particular laboratory--may indicate laboratory error, alteration of specimens (as from poor collection and/or storage techniques, such as evaporation), or an unusual patient population.


Statistical evaluation of method-comparison data. Comparison of two methods for determining a substance is a common procedure in clinical chemistry. Almost without exception, normal theory statistics are used with the tacit assumption that the data under test show gaussian distributions. Experience has led us to question this assumption for populations of differences between values obtained by two methods applied to common samples and for populations of paired values for each method as used in correlation analysis. Data are presented from our laboratory to illustrate these points, as well as an examination of data from relevant papers that appeared in this journal from 1968 through 1973. These examples indicate that incorrect interpretation of results because of insufficient attention to non-gaussian distribution is a real and present danger. We present a systematic approach to the statistical aspect of comparing methods that enables one to avoid this problem.


The impact of laboratory error on the normal range: a Bayesian model. Interpretation of clinical laboratory results, aside from clinical considerations, is based on the probability of the result being within a given normal range. This probability is influenced by the degree of error inherent in the analytical method. It would be advantageous to assign a more definite probability to the result of the measurement by combining the error distribution of the result around the true value and the distribution of the healthy population that serves as a reference. Bayesian statistics permits the revision of this prior information into a single probability.


Automated differentiation and measurement of hexosaminidase isoenzymes in biological fluids and its application to pre- and postnatal detection of Tay-Sachs disease. Three hexosaminidase (EC 3.2. 1.52) isoenzymes other than isoenzymes A and B in body fluids have been separated by chromatography on diethylaminoethyl cellulose. By inserting a microcolumn into a continuous-flow system for automated, fluorometric hexosaminidase analysis [Clin. Chem. 20, 538 (1974)], samples eluted with buffered-NaCl gradients can be continuously monitored. Isoenzyme patterns were obtained for fluids from normal individuals, pregnant women, Tay-Sachs disease carriers, pregnant carriers, and patients with the disease. These chromatograms revealed a hitherto undetected isoenzyme (I-3) in serum. An increase in serum hexosaminidase isoenzyme I-2 (or P) during pregnancy is characteristic of a carrier pattern. Our data show that serum and urinary hexosaminidase isoenzyme patterns may be used in addition to leukocyte analysis, to distinguish a pregnant carrier from a normal pregnant woman. All fluids tested demonstrated no isoenzyme A activity and above-normal activity of isoenzymes B and (or) I-2 in homozygotes. Urine is preferred fluid for postnatal and amniotic fluid for the prenatal diagnosis of the disease. Quantitative data on isoenzyme A obtained with the procedure described here agree well with those obtained by heat-and pH-inactivation methods.


Comparison of human pancreatic and parotid amylase activities on different substrates. The specific activities of highly purified preparations of human parotid and pancreatic amylase on several different soluble and insoluble starches were compared. The ratio of parotid to pancreatic activity varied with the physical nature of the substrate. With all soluble starches, irrespective of source, parotid amylase exhibited a higher specific activity than did pancreatic amylase; the reverse was true for an insoluble chromogenic starch (Amylose Azure). The variation in enzyme-substrate interaction supports previous indications of configurational differences between the two amylases. The observed organ-specific characteristics according to organ of origin may have value in determining relative parotid and pancreatic amylase activities in body fluids under normal and pathological conditions, thereby helping to clarify their functional and clinical significance.


Determination of orotic and dihydroorotic acids in biological fluids and tissues. In commonly used procedures for colorimetric assay of orotic acid in biological materials, certain substances interfere, positively or negatively. Some that interfere negatively are ornithine, cysteine, citrulline, tyrosine, proline, hydroxyproline, and polyamines. Protein and interfering agents are easily removed by first isolating the total organic acid fraction. The orotic acid in this fraction can then be determined by an established colorimetric procedure. A rapid liquid-liquid column-chromatographic procedure is described, if analysis of both dihydroorotic and orotic acid is required.


Interlaboratory comparison of enzymatic methods for serum glucose determination. This report describes an interlaboratory comparison of enzymatic serum glucose methods as currently applied in several instrumental adaptations. Four spectrophotometric, hexokinase-based methods used with the Du Pont "aca," the Abbott "Bichromatic Analyzer," the Aminco "Rotochem," and the Technicon "AutoAnalyzer ll" were compared with glucose oxidase-based methods as used with the Beckman "Glucose Analyzer" and the "AutoAnalyzer ll." We analyzed both normal samples and samples that contained potential interfering substances or were otherwise abnormal. Although all methods were satisfactorily precise, methodological bias was noted in several cases, particularly with abnormal specimens. The hexokinase-based methods were generally more variable. The most consistent data were obtained from the two glucose oxidase methods and the Du Pont aca. Results of this study comprise part of the background information required for development of an accurate glucose reference method under the auspices of the AACC Standards Committee.


Standardizing 125I sources and determing 125I counting efficiencies of well-type gamma counting systems. I describe the technique for determining the absolute decay rate of any 125I source. The problems of varying counting efficiency, varying sample geometry, and extended sources are discussed. By using the calibrated 125I source, the counting efficiency of the given counting system was obtained.


Electrophoresis on cellulose acetate and chromatography on DEAE-sephadex A-50 compared in the estimation of creatine kinase isoenzymes. We have compared two methods for separating the isoenzymes of creatine kinase in serum and measuring their activity: chromatography on diethylaminoethyl-Sephadex A-50, with both continuous and discontinuous gradient elution, and electrophoresis on cellulose acetate. Results by continuous and discontinuous gradient elution correlated well both for tissue extracts and sera. Electrophoresis on cellulose acetate is evidently less sensitive than the chromatographic method for detecting and measuring low activities of the isoenzyme designated MB. We describe how the isoenzymes may be separated by discontinuous gradient elution from microcolumns of the Sephadex and their activity rapidly quantitated by the Rosalki method [J. Lab. Clin. Med. 69, 696 (1967)], with a centrifugal analyzer.


Comparison of clinical assays for serum corticosteroids. We compared results obtained by (a) chemical (spectrophotometric) and competitive protein-binding assays for serum corticosteroids, and (b) competitive protein-binding and radioimmunoassay, with and without CCI-4 extraction, for serum cortisol. The two corticosteroid methods gave identical results. Radioimmunoassay with and without a CCI-4 extraction step gave identical results for cortisol. Competitive protein-binding assays for cortisol (with and without CCI-4 extraction) and radioimmunoassay for cortisol gave similar results. Specimens with above-normal corticosterone or 11-deoxycortisol concentrations are an exception: only methods that included CCI-4 extraction gave correct values for cortisol; methods without such an extraction step overestimated cortisol. The normal serum corticosteroid concentration (mean plus or minus SD) was 175 plus or minus 53 mug/liter for morning specimens, and 103 plus or minus 40 mug/liter for specimens collected in the afternoon. For cortisol, the corresponding values were 162 plus or minus 44 and 82 plus or minus 29 mug/liter.


Separation of creatine kinase isoenzymes in serum by ion-exchange column chromatography (Mercer's method, modified to increase sensitivity). We describe our experience with Mercer's method [Clin. Chem. 20, 36 (1974)] for separating isoenzymes of creatine kinase (EC 2.7.3.2) in serum by ion-exchange chromatography. By using diethylaminoethyl cellulose rather than diethylaminoethyl Sephadex in the column and by changing the ionic strength of the eluting buffer, we could detect a significant proportion of the MB isoenzyme of serum creatine kinase at normal activities of creatine kinase in serum, even in the absence of cardiac disease.


Improved biuret procedure for routine determination of urinary total proteins in clinical proteinuria. This communication describes and evaluates an improved routine methodology for quantitating clinical proteinuria. Based on investigations of Piscator and of Savory et al., a modified Tsuchiya's reagent (ethanolic HCI-phosphotungstic acid) is used to precipitate proteins at 56 degrees C, followed by biuret spectrophotometry at 540 nm. The accuracy  of the proposed procedure was assessed by comparisons with results obtained by using an ultrafiltration membrane that retains solutes with an average molecular weight in excess of 10 000 for separating of urinary proteins before they are measured with the biuret reaction. Precision of the method (coefficient of variation) is typically 2-3%.


Effect of albumin on serum digoxin radioimmunoassays. The use of certain commerically available radioimmunoassay kits for measurement of digoxin results in errors in the determined digoxin concentration of patients when these kits are used according to manufacturers' directions. One factor that is, in part, responsible for these errors is a difference between standards and samples with respect to albumin concentration. Three of the four kits investigated showed a significant inverse relationship between the albumin concentration in the sample and the binding of radiolabeled digoxin by its antibody when the albumin concentration was varied over an extended range. It is apparent, however, that differences in albumin concentration do not completely explain the observed variations in the assay values.


Use of nucleic acid hybridization for specific detection of submicrogram quantities of DNA, and its application to human plasma. A technique is described for using radiolabeled RNA complementary to human DNA as a probe for the specific identification of submicrogram concentrations of human DNA by formation of RNA-DNA hybrids. An example is given of its application to the semiquantitation of human DNA in human plasma, a substance that is ordinarily difficult to examine because materials are present that interfere with the usual colorimetric or fluorometric assays. An example is also given of the use of an analogous approach to analyzing rabbit serum for circulating bacterial DNA. Unique to the hybridization technique is a degree of specificity sufficient to identify specific base sequences and hence the origin of the DNA being detected, a point that may be important in the examination of circulating DNA reported to occur in patients with systemic lupus erythematosis. This technique may also be of value in clarifying the presently conflicting data regarding the occurrence of free DNA in the normal human circulation.


Free amino acids in human tonsillar tissue. Free amino acids in the tonsils of 20 individuals were measured column chromatographically. Those always found in readily detectable amounts included O-phosphoserine, taurine, O-phosphoethanolamine, aspartic acid, hydroxyproline, threonine, serine, glutamic acid, proline, glycine, alanine, alpha-amino-n-butyric acid, valine, cystine, methionine, isoleucine, leucine, tyrosine, phenylalanine, ornithine, gamma-amino-butyric acid, lysine, histidine, and arginine. Results were compared for three clinical pathological groups and for four age groups. Some abnormal values may result from the pathological conditions.


Comparison of results for morphine urinalyses by radioimmunoassay and thin-layer chromatography in a narcotic clinic setting. Radioimmunoassay (RIA) and thin-layer chromatography (TLC) were compared for morphine detection in an actual narcotic clinic setting. A choice of urines from all those screened by TLC allowed a critical comparison as to actual use or non-use of narcotic drugs, rather than a sampling at random in which the question of possible false positives or negatives cannot be conclusively answered. Although RIA is more sensitive than TLC, its advantage is apparent only in those cases where urine specimens are difficult to obtain frequently regularly or where the use of morphine is suspected by the positive identification of quinine in urine that was morphine-negative by TLC. In a selected group of negative and positive specimens chosen without conscious bias, the two methods gave consistently similar results, indicating that the modified TLC method provided a few or no false positives or negatives if the negatives were from those cases that were not positive anytime up to 3-4 days before urine collection. We conclude that RIA can be of significant value as a supplement to a TLC screening program, without sacrificing the many advantages that TLC has to offer.


Lipase-triggered kinetic assay of serum triglycerides. We describe a kinetic method for assay of serum or plasma triglycerides, by use of an enzymatic hydrolysis and reaction sequence already described [Clin. Chem. 19, 476 (1973)]. The reaction is triggered by addition of lipase, at a time when free glycerol, or pyruvate (or both) are no longer present. In this method, therefore, there is no need for a blank glycerol assay. In the procedure, reagents are used that are available commercially in the form of stable, dry powders; the method for the preparation of the reagents has been changed to achieve improved stability and performance. Stability and recovery of added triglycerides are satisfactory.


Simultaneous determination of serum cholesterol and triglycerides after preliminary column chromatography. An isopropanolic extract of serum can be made suitable for the simultaneous estimation of cholesterol and triglycerides by passing it through a commercially-available chromatographic column containing activated metallic oxides in which alumina predominates. No centrifugation step nor phase separation is required. Use of the purified extract allows existing methods to be simplified and shortened without loss of reproducibility or stability. Results compare well with those obtained by traditional methods.


Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies. Investigation of a psychomotorically retarded girl showed excretion of abnormal amounts of alpha-ketoadipic acid, alpha-hydroxyadipic acid, alpha-aminoadipic acid, 1,2-butenedicarboxylic acid and elevation of plasma alpha-aminoadipic acid levels.  The identity of these metabolities was established by various methods.  The excretion of alpha-aminoadipic acid correlated to the lysine intake.  Degradation studies with cultured fibroblasts indicate a defect in the oxidative decarboxylation of alpha-ketoadipic acid (see Clin. Chim. Acta, 58 (1975) 271.


Alpha-ketoadipic aciduria: degradation studies with fibroblasts,. Observation of one patient with alpha-ketoadipic aciduria initiated degradation studies with radiolabelled lysine metabolites in fibroblasts in order to localise the metabolic defect. Liberation of 14-CO-2 from alpha-D,L-(1-14-C) aminoadipate and alpha-(1-14-C) ketoadipate was considerably less in the patient's fibroblasts than in the patient's fibroblasts than in normal controls, whereas 14-CO-2 production from (1,5-14-C) glutarate was in the normal range. These results indicate a defect in the oxidative decarboxylation of alpha-ketoadipate as the probable cause of alpha-ketoadipic aciduria; Cultured amniotic fluid cells from pregnancies of the 15th and 16th week of gestation degrade alpha-(1-14-C) ketoadipate with a similar activity to fibroblast cultures from normal humans after birth.


Erythrocyte adenosine deaminase and purine nucleoside phosphorylase activity in gout. 1. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine nucleoside (inosine) phosphorylase (EC 2.4.1.1) were measured in 33 healthy controls and 43 primary gouty subjects. Adenosine deaminase activity in controls and gouty subjects was 0.373 plus or minus 0.108 and 0.457 plus or minus 0.140  A unit per 5-10-3 ml packed red cells per h, respectively. The difference was statistically significant (P less than 0.01). Mean adenosine deaminase: inosine phosphorylase (X10) in primary gout was also significantly higher than in controls (P less than 0.05). Inosine phosphorylase activities in the two groups were not significantly different. 2. When gouty patients were divided into two groups according to weight, normal weight gouty subjects had a higher adenosine deaminase activity and an increased ration of adenosine deaminase to inosine phosphorylase when compared with overweight patients (P less than 0.10). In two control groups divided according to the percentage overweight, such differences were not found. In the case of two gouty groups divided according to the existence of gouty heredity, tophi or renal impairment, adenosine deaminase and inosine phosphorylase activity in the two groups were not significantly different. The possible biochemical role of adenosine deaminase activity in primary gout is discussed.


A simple automated micromethod for measuring serum copper. An automated micromethod for measuring copper concentration in 0.2 ml of serum employing formaldehyde-oxalydihydrazide as chromogen and using an Auto-Analyzer (Technicon) is presented. The use of formaldehyde-oxalyldihydrazide resulted in a stable and noise-free baseline. The coefficient of variation of the micromethod was 2.4%. The recovery of copper added to samples was 102%. A good correlation between the serum values estimated by the described method and the manual method of Summers (1) (r = 0.929; P less than 0.001) was found when copper standards were prepared in 0.277 M glucose. The mean serum copper concentration found in 26 healthy adult males is 94.1 mug/dl (range: 80 to 120 mug/dl) and in 20 females is 109.8 mug/dl (range: 71 to 170 mug/dl), the difference being statistically significnt (P less than 0.02).


Adolescents with developmental disabilities; a survey of their problems and their management. Adolescents with developmental disabilities deserve the same sophisticated multidisciplinary evaluation which is now available to younger children. Most of these fit into one of four groupslow normal IQ with poor performance because of psychologic problems, true learning disability, neuromuscular disease, or known mental retardation in need of planning for future care. It is important for the physician dealing with these adolescents to recognize and be ready to deal with the high incidence of emotional problems. He must be able to relate to the adolescents as the primary subject, and to arrange special education, vocational evaluation, and legal counseling. The physician must cultivate professional relationships with a wide range of disciplines since his adolescent patient is likely to need a wide variety of services.


Larsen's syndrome;.

Larsen's syndrome;. Three cases of Larsen's syndrome with retospective diagnoses have been described. All of them had both the clinical and radiographic signs characteristic for the syndrome, namely flat, hyperteloric facies, multiple dislocations of the joints, club foot deformity, and long cylindrical fingers. The radiographic findings were generalized and diagnostic in all of the cases. Our patients had additional ossification centers for the body of calcaneus.


The atherosclerosis problem: pediatric and dietary aspects. Arteriosclerotic vascular disease begins in childhood. This most common and serious disorder must be of concern to all those caring for the health of children. Consideration should be given to the possibilities of altering the basic American diet to one lower in saturated fats and cholesterol.


Cardiogenic oscillations of nitrogen and argon concentration in expired gas in man. 1. The cardiogenic oscillations in the concentration of nitrogen and argon in expired gas, which are seen after the inspiration from residual volume of pure oxygen or a bolus of argon, have been studied in normal subjects and in patients with atrial fibrillation. 2. In the upright position of the subject, the peaks of nitrogen and argon concentration coincide with ventricular systole, although there is a transit delay along the tracheobronchial tree before any change of concentration occurs at the mouth. 3. Studies in different postures demonstrated that the effect of the heart is predominantly due to a reduction in cardiac volume during systole with a decrease in airflow from regions adjacent to the heart. These areas contain a different concentration of nitrogen and argon in the alveolar air from the more apical regions. 4. It has been shown that the results are consistent with the present concepts of the influence of gravity on the distribution of inspired air.


Measurement of intrarenal blood-flow distribution in the rabbit using radioactive microspheres. 1. Total renal blood flow and its distribution within the renal cortex of the conscious rabbit were studied with radioactive microspheres of 15 and 25 mum diameter. 2. The reliability of the microsphere technique was influenced by microsphere diameter and number (dose). The optimum microsphere diameter for determination of flow distribution in the rabbit kidney was 15 mum and dose 100-150 000 spheres. 3. Spheres of 15 mum nominal diameter were randomly distributed within the renal cortex of adult rabbits. The larger spheres in batches nominally 15 mum in diameter in young rabbits and 25 mum diameter in adult rabbits were preferentially distributed to the superficial cortex. 4. In adult rabbits 15 mum diameter spheres lodged in glomerular capillaries. Larger spheres occasionally lodged in interlobular arteries causing intrarenal haemorrhage. 5. Microspheres of 15 mum caused a decrease in renal clearance of creatinine and of p-amino-hippurate when the total injection dose was about 200 000 spheres. These effects were greater when the injection dose was increased to 500 000 spheres. 6. The reduction in total renal blood flow observed with large doses of spheres largely reflected decreased outer cortical flow, as measured by a second injection of spheres, and confirmed by a decrease in p-aminohippurate extraction. 7. The reproducibility of multiple injection studies was limited by these intrarenal effects of microspheres. 8. Total renal blood flow measured in six rabbits in acute experiments by the microsphere technique was 107 plus or minus 12 (mean plus or minus SD) ml/min and by p-amino-hippurate clearance was 100 plus or minus 10 ml/min. 9. Total renal blood flow in twelve conscious, chronically instrumented rabbits was 125 plus or minus 11 ml/min, of which 92 plus or minus 6 ml/min was distributed to the superficial cortex and 33 plus or minus 4 ml/min to the deep cortex.


Renal circulatory responses to general anaesthesia in the rabbit: studies using radioactive microspheres. 1. Total renal blood flow and its cortical distribution were measured by the radioactive microsphere technique in conscious rabbits and after anaethesia with pentobarbitone, chloralose-urethane or ether. 2. Pentobarbitone anaesthesia caused a fall of 26% in total renal blood flow, of 26% in superficial cortical flow, and of 24% in deep cortical flow. Sodium excretion rate fell by 33%. 3. Chloralose-urethane anaesthesia caused no change in total or regional renal blood flow, or in sodium excretion. 4. Ether anaesthesia caused an insignificant fall in total renal blood flow, but superficial cortical flow fell by 13% and deep cortical flow rose by 21%. Urinary sodium excretion fell by 65%. 5. Possible mechanisms for these changes in response to anaesthesia are discussed. 6. The effects of anaesthetic agents may influence the interpretation of published work on control mechanisms in the renal circulation.


Uranyl nitrate acute renal failure in the dog: early changes in renal function and haemodynamics. 1. Sodium excretion, plasma renin acitivity (PRA), inulin clearance, total renal blood flow (RBF), renal cortical radiomicrosphere distribution and systemic administration of uranyl nitrate (19.9 mumol/kg body wt.; 10 mg/kg) in the dog. 2. During the 3 h of study after uranyl nitrate, urine flow remained stable or increased, sodium excretion increased approximately fivefold, renal vascular resistance increased threefold, and concordant decreases in RBF and inulin clearance to 40-50% of control values occured. At 3 h total cortical RBF decreased to 35% of control values and the ration of blood flow in outer to inner cortical zones also decreased, reflecting outer cortical ischaemia, PRA increased in the first hour after uranyl nitrate and slowly declined therafter, though not to control values. 3. Respiratory rate, heart rate, mean systemic blood pressure and cardiac output were unchanged after uranyl nitrate, demonstrating that the changes in renal vascular resistance occurred without a change in peripheral vascular resistance. 4. It is postulated that increased renin-angiotensin system activity mediates the change in renal haemodynamics and the consequent fall in glomerular filtration.


Using polar coordinates to measure variability in samples of Phenacolemur: a method of approach. Polar coordinates can be used to quantify shapes on which homologous points cannot be readily identified such as lophs, edges, circumferences, outlines of areas, etc., This allows one to describe quantitatively characters, often diagnostic, that at present are not usually quantified and hence do not figure in the statistical analysis of variability that ought to accompany morphological descriptions in taxonomic work. Computer-driven plotters, using this data, provide an efficient means of graphing it, with great accuracy, in a variety of ways that can be used as an aid in qualitatively assessing variability in a sample or as a basis for further quantitative work. Principal component analysis of the data is essential to reduce the great quantity of measurements to a more manageable amount. It is also a valuable aid in interpreting the information. In the example using the Phenacolemur sample, it was shown with the data obtained from the use of polar coordinates in measuring that: (1) Discriminant functions can be used to distinguish between teeth that are very similar in shape and size, such as the Phenacolemur M1 and M2 and with which it is difficult to make such a distinction visually in an objective fashion. (2) It can be shown quantitatively that size is the only valid distinguishing criterion in splitting the AMNH Phenacolemur sample into three species and that the variability in shape is not significant.


Rheumatoid arthritis in a dog.

Rheumatoid arthritis in a dog. Rheumatoid arthritis was diagnosed in a 5-year-old  Golden Retriever. Diagnosis was made on the basis of historoclinical, laboratory, and radiographic findings, a positive rheumatoid factor titre, and compliance with the American Rheumatism Association criteria for diagnosis of rheumatoid arthritis in man. Satisfactory remission was obtained with buffered aspirin.


Partial lobectomy of bovine liver: a new biopsy technique. A surgical technique has been developed for partial lobectomy of the bovine liver to obtain greater than 25 gram liver samples. Vertical mattress sutures, backed with plastic tubing, were replaced in the liver near the incision line to provide hemostasis. Hemostasis of the cut surface of the liver was adequate in each case. Postoperative recovery was uneventful and only minor adhesions were found later by laparotomy and at necropsy.


Peripheral plasma levels of progesterone and fertility after prostaglandin-2alpha induced oestrus in heifers. Sixteen heifers of the Swedish Red and White Breed were given 25 mg PGF2 alpha as tromethamine salt intramuscularly or subcutaneously either on day 8 or day 14 of the oestrus cycle. The injection of PGF2 alpha caused a marked reduction of the size of the corpus luteum in 24 hours. Irrespective of day of injection standing heat occurred 48-96 hours after administration of PGF2 alpha. In the heifers injected on day 8 of the oestrus cycle the midcycle follicle continued to grow and appeared to be the one which was ovulated. Inheifers injected on day 14 a new follicle could be palpated within two days. Eleven of the 16 heifers (69%) became pregnant during the induced heat period. All heifers showed a marked decrease of the peripheral plasma level of progesterone on the day after treatment. The mean progesterone level at the day of first insemination was 80 pg/ml and at the day of second insemination where applied 46 pg/ml. It is concluded that intramuscular or subcutaneous administration of PFG2 alpha on days 8 and 14 of the oestrus cycle results in luteolysis of the cyclic corpus luteum, follicular growth, ovulation and normal pregnancy result after artificial insemination.


Hypercalcemia and calcinosis in Florida horses: implication of the shrub, Cestrum diurnum, as the causative agent. A chronic debilitating disease is described in Florida horses. There is progress weight loss and lameness of increasing severity. Plasma calcium is elevated to moderate or severe degree. Anatomical changes include dystrophic calcinosis of elastic tissues, viz. major arteries, tendons and ligaments. A generalized osteopetrosis is present and may be related to hypoparathyroidsim and hypercalcitoninism. The presence of Cestrum diurnum (day-blooming jessamine, day cestrum, wild jasmin) in areas accessible to affected animals, the observation that leaves of the plant were stripped in these areas, and the finding of a potent, active vitamin D-like substance in this plant constitute strong evidence that Cestrum diurnum is the agent causing the abnormalities of mineral metabolism.


Castration and other factors affecting the risk of equine laminitis. The characteristics of a series of equine laminitis cases were compared with that of other Equidae examined at the University of Missouri Veterinary Hospital and Clinic during May, 1965 through December, 1971. The model age for ponies with laminitis was 7-9 years and for all other cases the model age was 4-6 years. Also the predominant age for mares was 4-6 years and for males was 7-9 years. After controlling for age and breed differences, there were significantly fewer castrated males among the affected males than expected (P small than 0.02), indicating that hormonal factors may play a role in laminitis. Ponies had a significantly greater risk of laminitis (P smaller than 0.001) and their relative risk was 4.3 times greater than all other Equidae combined. There were more laminitis cases diagnosed during May than during other months.


A study of immunologic relationships among serologically heterologous strains of bovine viral diarrhea virus by cross immunity tests. Three serologically heterologous strains of bovine viral diarrhea (BVD) virus were compared in reciprocal cross immunity tests in calves. Each strain was inoculated into five calves. Thirty-eight days later one calf in each group was reinoculated with homologous virus while the immunity of the remaining four was challenged with the serologically heterologous strains of virus, using two calves for each strain. Of the 12 calves in the cross immunity tests, nine were refractory to immunity challenge with the heterologous viral strains while one in each group responded with mild, atypical signs of BVD. On the basis of immunity testing it appears that significant serologic differences among strains of BVD virus are unrelated to the immunologic properties of the strains. It was demonstrated, moreover, that each of the three strains used in the present study evoked the production of antibody to the heterologous as well as to the homologous strain of virus.


Intersynovial fistula in the carpus of a horse. Soft tissue lesions are often secondary  to equine carpal injury. The clinical and pathological nature of soft tissue changes following carpal trauma are varied. This report describes a case of intersynovial fistula between the radial carpal joint and the common digital extensor tendon sheath. The differential diagnosis and pathological features of equine soft tissue carpal injuries are discussed.


Growth and aging of the normal human lung. The lung grows primarily by alveolar multiplication, but alveoli also double in size from infancy to adult life. The time at which alveolar multiplication ceases is obscure. As the lung ages it loses alveolar surface area due to alteration in the internal geometry of the lung. Alveolar wall tissue is also lost, thought to reflect loss of capillary bed.


Isolation of pulmonary pressor substances from bovine amniotic fluid. The pulmonary pressor activity of bovine amniotic fluid resides in substances that appear to be non-polar lipids as suggested by the various chemical and chromatographic procedures. In preliminary experiments, it was found that the pressor activities of the hexane extracts were blocked by prior administration of aspirin to the calf (1 mg/kg), suggesting that pressor effect was mediated via the prostaglandin system. The amniotic fluid lipids, however, differed from the known prostaglandins in being less polar as indicated by thin layer chromatography and in possessing greater pressor activity. It is possible, of course, that the lipids with pulmonary pressor activity participate in the metabolism of the prostaglandins.


Return of arterial PO2 values to baseline after supplemental oxygen in patients with cardiac disease. Serial arterial PO-2 values were obtained following discontinuation of supplemental inspiratory oxygen by face mask in 21 patients suffering from a variety of cardiac diseases. All patients were free of pulmonary disease. Arterial PO2 values returned to baseline within seven minutes after supplemental oxygen was withdrawn. Decay rate constants calculated from the arterial PO2 measurements were unaffected by cardiac index or the level of pulmonary capillary wedge pressure. We conclude that in patients free of overt pulmonary disease, arterial PO2 measured five to seven minutes after withdrawal of supplemental inspiratory oxygen accurately reflects an individual patient's baseline arterial PO2 value.


Prolonged rate of decay of arterial PO2 following oxygen breathing in chronic airways obstruction. Nine patients with moderate to severe chronic obstructive lung disease were grouped according to results of pulmonary function testing. After a short period of 100 percent oxygen breathing, it took on the average 20 minutes (range--18 to 24 minutes) for their partial pressure of arterial oxygen to return to baseline levels. These data suggest that, after discontinuing supplemental oxygen in patients with chronic airways obstruction, more than 25 minutes should elapse if a blood gas measurement is to reflect with certainty conditions during room air breathing.


Comparison of 24 versus 12 hours of ambulatory ECG monitoring. In order to assess the additional information obtained from 24 hours compared to 12 hours of ambulatory ECG (electrocardiogram) recording, we analyzed 72 ambulatory ECG monitoring tapes in which arrhythmias were present. In all cases the second 12 hours included the entire period of sleep. Only 38 of 233 (16 percent) episodes of arrhythmias, frequent premature ventricular contractions (PVC's), two or more PVC's in a row, multiform PVC's, ventricular bigeminy, trigeminy, premature atrial contractions (PAC's), and supraventricular tachyarrhythmias occurred for the first time in the second 12-hour period. New ventricular arrhythmias were detected during the second 12-hour period in 13 percent of the arrhythmic episodes. Although sleep resulted in a marked decrease in PVC frequency in 63 percent of 30 recordings, with frequent PVC's while awake, 8 percent had a significant increase during sleep. In contrast, short runs of supraventricular tachyarrhythmias occurred during the second 12 hours in 48 percent of cases, 66 percent of these while asleep. These data suggest that a 24-hour ambulatory ECG tape recording be utilized initially to characterize the occurrence and frquency of the patients' ambulatory arrhythmias during awake and sleep periods. Thereafter, additional ECG recordings for monitoring antiarrhythmic drug therapy can be accomplished with a 12-hour recording in more than 80 percent of patients


Pacemaker implantation based on ambulatory ECG monitoring in patients with cerebral symptoms. Continuous ambulatory ECG monitoring was performed in 110 patients because of a history of dizziness, alleged syncope of vague cerebral manifestations. The resting ECG failed to provide an explanation for symptoms in any of the patients. In 12 patients the monitoring revealed a variety of arrhythmic mechanisms which required pacemaker implantation. Five of these patients had sick sinus syndrome with episodes of prolonged sinus arrest, while in the others various degrees of A-V block were detected. Implantation of a pacemaker relieved the symptoms in all. It is concluded that ambulatory ECG monitoring is essential in evaluating cases of unexplained cerebral symptoms.


Effect of propranolol on respiratory function and exercise tolerance in patients with chronic obstructive lung disease. Ten patients with chronic obstructive lung disease (COLD) (group 1) and five patients with combined COLD and cardiac disease (group 2) were studied at rest and during exercise after an intravenous (IV) slaine control followed by IV propranolol (0.2 mg/kg). During rest propranolol did not alter significantly measurements of lung volume in groups 1 or 2. Following propranolol the mean airway resistance (AR) in group 1 increased from 4.49 to 5.2 cm H2O/L/sec (P smaller than 0.02) and airway conductance (Gaw) decreased from 0.28 to 0.24 L/sec-1 cm. H2O1 (P smaller than 0.02). In group 2 following propranolol, the mean AR increased from 3.60 to 4.67 cm H2O1 (P smaller than 0.05), and Gaw decreased from 0.30 to 0.23 L/sec-1/cm H2O1 (P smaller than 0.05). During exercise, from control to propranolol, the heart rate (HR), blood pressure (BP), and heart rate blood pressure (HR x BP) decreased significantly for both groups 1 and 2 except for the systolic pressure in group 2. The duration of exercise and exercising PO2 were not significantly altered from control to propranolol in groups 1 and 2, indicating that the small but statistically significant changes in AR and Gaw did not interfere with symptom tolerated maximal exercise in these patients and were therefore not clinically important.


Prognostic significance of chronic versus acute bundle branch block in acute myocardial infarction. Of 1125 patients with acute myocardial infarction admitted to Mount Sinai Medical Center in 1971 and 1972, 292 (28.8 percent) had intraventricular conduction defects. In 210 of the 292 patients with intraventricular conduction defect, it was possible to determine if the conduction defect, was present before the infarction (Group 1, 123 patients) or developed acutely with the infarction (Group 2, 87 patients). Of the 210 patients, 52.8 percent died (mean age 72.1 years). Fifty-three patients in Group 1 and 18 patients in Group 2 had isolated left axis deviation (LAD). The mortality was 35 percent and 28 percent respectively. This difference was not significant (p greater than 0.60). Sixty-four of the 210 patients presented with a left bundle branch block (LBBB) pattern. The overall mortality of 54 percent was the same in both groups. Right bundle branch block(RBBB), with either normal axis, left (LAD) or right axis deviation (RAD), was found in 74 patients. Of 40 patients in Group 1, 62 percent died, and of 35 patients in Group 2, 80 percent expired. Again this difference was not significant (p greater than 0.10). In 13 of 25 patients with RBBB in Group 1, death was possible related to progression of the conduction defect. The use of prophylactic temporary pacing is suggested for these patients.


Unmasking of slow intrinsic ventricular excitation by magnetic inhibition of R-wave inhibited demand pacemakers. In patients with permanent pacemakers and slow intrinsic ventricular excitation, the pacemaker rhythm dominates ventricular excitation. Diagnostic considerations may require that the electrocardiographic morphology of the intrinsic beats be known, such as during the exclusion of the myocardial infarction. If the pacemaker is a Cordis R wave inhibited (Stanicor) type, it is possible to allow the intrinsic rhythm to emerge by external magnetic inhibition of the pacemaker. Such inhibition can be achieved by rotating a magnet back and forth through a 180 degree arc with the magnetized poles on the surface of the chest wall above the pacing unit. Successful pacemaker inhibition by the magnet will abolish the pacemaker rhythm. It is concluded that magnetic inhibition of R wave inhibited pacemakers may be a useful diagnostic tool in patients with Stanicor pacemaker rhythms.


Fatal lung scan in a case of pulmonary hypertension due to obliterative pulmonary vascular disease. A young woman with pulmonary hypertension due to sclerodermatous pulmonary vascular disease died immediately following the injection of macroaggregated albumin labeled with 99-TC for a perfusion lung scan. Review of the literature suggests that patients with chronic pulmonary hypertension due to an obliterative pulmonary vascular disease are at risk of developing a serious reaction to perfusion lung scanning. Important factors which predispose to an adverse reaction to lung scanning are the size and dose of macroaggregated albumin particles in relation to the total cross-sectional area of the pulmonary vascular bed and a critical arteriolar lumen size.


The unreliability of the maximal midexpiratory flow as an index of acute airway changes. This study evaluates the reliability of the maximal midexpiratory flow (MMF) as an index of acute airway changes. In a group of asthmatics, intravenous histamine induced a significant decrease in the forced vital capacity, expiratory volume in the first second, and peak flow, while increasing the respiratory system resistance and the closing volume. The studies showed narrowing of the airways, while the MMF significantly increased in all subjects, implying dilation of the airways. The increased closing volume suggested narrowing of the small airways. The data, however, suggest that the paradoxic increase of the MMF is a result of histamine-induced early small airway closure, eliminating the lung units with longer time constants. Unless the MMF is related to absolute lung volumes (as presently measured the MMF is not related to absolute lung volumes) it may be misleading, and is thus an unreliable index of acute airway changes.


Left subclavian steal, interrupted aortic arch, complete transposition of the great vessels and single left ventricle. Congenital subclavian steal consists of atresia of the proximal end of the subclavian artery, while the blood supply to the distal portion of the subclavian artery originates from the circle of Willis. It should be suspected in complicated malformations of the heart associated with marked hypoplasia or interruption of the aortic arch. Minimal differences in blood pressure determinations may be an important clue in the diagnosis of this anomaly. The diagnosis may be confirmed by angiography with careful attention to late arterial phase films.


Strangulation of the left atrial appendage through a congenital partial pericardial defect. The first case of strangulation of a left atrial appendage through a partial congenital pericardial defect is presented. Surgery consisted of a left atrial appendectomy and closure of the defect.


Resolution of an iatrogenic coronary artery thromboembolus. A patient with an iatrogenic coronary thromboemboulus, sustained during selective left coronary catheterization is presented. The embolus was identified by angiography and its complete resolution was documented in the same manner three months later. Despite chest pain and elevation of the cardiac enzymes, the electrocardiogram showed only nonspecific changes and the absence of macroscopically identifiable infarction was demonstrated at thoracotomy. Thromboembolization may be a more common cause of complication with the Judkins technique than generally realized but may be compatible with complete recovery and be avoided by special catheterization practices.


Successful surgical resection of a chronic false aneurysm of the left ventricle. The case of a patient with a chronic false aneurysm of the left ventricle diagnosed three years after a documented myocardial infarction is reported. The patient presented with a mass seen on the chest x-ray examination. The correct diagnosis was made by ventriculography and the aneurysm was successfully resected.


Coronary artery to left atrial fistula in association with severe atherosclerosis and mitral stenosis: report of surgical repair. Not uncommonly, atherosclerosis may be found associated with rheumatic heart disease. The combination of atherosclerosis, rheumatic heart disease and coronary fistula is an unusual combination of hemodynamic and disease states. We report a patient with advanced mitral stenosis and atherosclerosis who also had a fistula from the left coronary artery into the left atrium. Surgical approach: combined valve replacement, bypass grafting and closure of the fistula in an attempt to relieve the pathophysiologic abnormalities.


Hypoglycemia complicating the use of solution of glucose, insulin and potassium. A patient is described who developed hypoglycemia and generalized neurologic depression after cardiac surgery, while receiving an infusion of glucose, insulin, and potassium (GIK). Hypoglycemia as a complication of the use of GIK solution in patients with hepatic dysfunction, malnutrition and low cardiac output is discussed.


Palsy of the recurrent nerve following mediastinoscopy. As demonstrated in earlier material, the frequency of palsy of the recurrent nerve following mediastinoscopy varies from 0.18 to 0.53 percent (17,000 patients). In 67 patients operated via mediastinoscopy, where pre- and postoperation indirect laryngoscopy was carried out, four postoperative palsies (6 percent) were discovered. Of these, 3 were found among the 24 patients with malignant infiltration of the mediastinum. The value of pre- and postoperation examination of the larynx is stressed.


Miliary tuberculosis presenting as acute respiratory failure: treatment by membrane oxygenator and ventricle pump. A 58-year-old woman with high fever, dyspnea, rapidly progressive hypoxemia and opacification of the lung fields presented the clinical picture of catastrophic respiratory failure. Extracorporeal support of oxygenation using a membrane oxygenator and a new ventricle pump was initially successful. At autopsy, miliary tuberculosis was found to be the cause of this "shock lung like" syndrome.


Infarct of the myocardium with aneurysm in a 13-year-old girl. We present the case of a girl with an infarct and an aneurysm of the left ventricle after viral disease at the age of six years. She died suddenly at 13 years of age. Autopsy findings revealed occlusion of the anterior descending and narrowing of the right coronary artery. The possible relationship of virus disease to the vascular disease is discussed.


Vanillyl mandelic acid excretion in unilateral electroconvulsive therapy (ECT). The twenty-four hour urinary excretion of vanillyl mandelic acid was determined in a group of eleven psychiatric patients prior to and during the day of the fifth unilateral electroconvulsive treatment. The patients were all determined by their treating psychiatrists and by psychological testing to be psychotically depressed. In ten of the eleven patients a marked decrease in excreted vanillyl mandelic acid was apparent from the pretreatment level to the fifth treatment level. In one of the eleven patients there was a slight rise from the pretreatment level to the excreted level during the fifth day of treatment. The mean pretreatment determination of vanillyl mandelic acid was 4.2 mg per twenty-four hours; the mean determination made on the fifth treatment was 2.8 mg per twenty-four hours.


Patterns of symptom change in anxious depressed outpatients treated with different drugs. Patients with mixtures of anxiety and depressive mood of rather modest degree constitute a majority in the psychiatric outpatient population. Drug treatments are employed to produce symptomatic relief. In this study, thirteen commonly used psychotherapeutic drugs were compared for efficacy in producing change in symptoms of anxiety, depressive mood, and psychomotor activation level in this most common type of psychiatric clinic patient. The drugs were found to differ in relative effect on anxiety and depressive mood. Paradoxically, the major and minor tranquilizers produced greater effect on depressive mood than anxiety, while the more sedative of the tricyclic antidepressants produced relatively greater effect on anxiety. Within each of the three major drug classes, the more sedative members of the class tended to have relatively greater effect on anxiety and the less sedative tended to have relatively greater effect on depressive mood components of the symptom picture.


Self-identification and the underdetection of alcoholism. Data obtained from administration of the Michigan Alcoholism Screening Test (MAST) to 66 institutionalized male alcoholics supported the hypothesis that MAST items which reflected alcoholic self-identification were more likely to result in underdetection of alcoholism than the other MAST items. These findings supported the contention that one of the consequences of devising and validating the tests on self-acknowledged alcoholics is the underdetection of cases. Implications for planning and delivery of alcoholism programs are suggested. The process by which alcoholism screening tests are developed and validated is frequently such that those items are selected which differentiate between a grouping of subjects known to be alcoholics (for example, patients on an alcoholism treatment ward) and a comparison grouping of subjects who are presumed to be free of alcoholism. However, it is questionable whether the alcoholism criterion grouping employed in this process is representative of the universe of alcoholics. The very process of becoming part of a known alcoholic grouping generally involves being identified as an alcoholic and referred for treatment by others (family members, physicians, etc.) and/or oneself. The criterion grouping therefore might include only self-identified alcoholics and exclude alcoholics who were able to avoid detection and self-perceptions of having an alcoholism problem. Consequently the items which are included in the screening test by virtue of differentiating between the criterion group and the comparison group might reflect the phenomenon of self-identification with alcoholism rather than a more broadly defined alcoholic condition. Among the possible consequences of this situation is the underdetection of cases since the screening test would tend to detect instances of self-identified alcoholism to the exclusion of non-self-identified alcoholism. In a prior analysis of data described elsewhere it was determined that a particular screening test -the Michigan Alcoholism Screening Test (MAST) - does appear to reflect alcoholic self-identification instead of, or as well as, a more inclusively defined alcoholic condition. However, it remained to be determined whether or not this situation would indeed result in the underdetection of alcoholics since the possibility existed that "self-identified alcoholism" and a presumably more inclusive "condition of alcoholism" were in fact coterminous categories. This paper deals with the latter issue.


Pimozide in chronic schizophrenic outpatients. In a double blind placebo controlled clinical evaluation of maintenance therapy in chronic schizophrenic female outpatients, thiordazine in single daily doses not exceeding 375 mg./day for 6 months was shown to be effective maintenance treatment compared with PL, thereby establishing the sensitivity of the experiment. Pimozide was also shown to be effective in a single oral dose not exceeding 16 mg./day and comparable overall to the standard drug. The experimental design was based on the anticipated retrogression of PL treated subjects during the 6-month study period, which was reflected in 5 of 9 (56%) "treatment failures" in the PL group compared to 2 of 14 (14%) and 2 of 12 (17%) in the THI and PIM groups, respectively. In addition, in some instances improvement over baseline evaluations was noted in both drug groups, particularly on global impression. Though some items of the BPRS exhibited Drug: PL differences, the scale in general was felt to be rather insensitive for this kind of study. Social adjustment ratings on a special scale completed by the patients and families alike, were also found to be insensitive to treatment differences. Side effects most often seen with THI were sedation, EKG and liver function abnormalities. Headache and restlessness occurred most often with PIM. Extrapyramidal symptoms and insomnia were seen most often with PIM and PL equally.


Atypical signs of relapse in affective disorders. The authors have observed that patients with previous well documented evidence of affective illness can have an atypical relapse of depression precipitated by environmental or interpersonal stress. These patients present with complaints centered around problems resulting from current life stress. They deny sad mood and resist the idea that they are having recurrence of depression. It is suggested that the presence of anhedonia be used as a clinical guide to differentiate "understandable" preoccupation with reality problems from emergent depressive relapse. Patients with atypical relapses respond to antidepressants with a disappearance of anhedonia and an ability to place realistic problems in their proper perspective. Cases are presented illustrating this phenomena.


[HL-A, W 27 and serum amino-acids in ankylosing spondylitis (author's transl)]. Tests for HL-A, W 27 were positive in eight of twelve patients with ankylosing spondylitis. The four negative cases, among them three members of the same family, had a different antigen pattern. Also positive were two cases with Reiter's disease. Semi-quantitative determination of serum levels of aminoacids in this group gave an increased alanine concentration in all but two instances. Leucine and valine levels were also raised, but less characteristically than alanine. These immunogenetic studies enrich diagnostic possibilities in clinical medicine, in addition to suggesting a possible common aetiology and(or) pathogenesis of Reiterś disease and ankylosing spondylitis. The significance of quantitative amino-acid modifications is not clear.


[Left atrial lead and stimulation in wpw-syndrome type A (author's transl)]. Normal and accessory A-V conduction were analyzed by His bundle recordings in a 49-year-old patient with WPW-syndrome type A. An open foramen ovale permitted registration of left atrial potentials as well as left atrial pacing. The effects of the pacemaker site (left or right atrial pacing) on the electrocardiographic variability of pre-excitation were studied. The effective refractory period of the accessory A-V conduction was shown to be dependent on the site of pacing. Recordings of right and left atrial potentials during runs of supraventricular tachycardia demonstrated that V-A conduction occurred via the accessory pathway.


[Is goiter an endemic disease in the German Federal Republic? (AUTHOR'S TRANSL)]. Statistical analysis of indexed information on 5,4 million men, subject to military conscription, gave a goitre incidence of 15.29 per cent. This corresponds to an endemic state and would suggest that goitre prevention programme is needed.


[Breast cancer in women as a paradigm for ageing as a hidden syncarcinogenic factor]. In man the application of so-called cancerogenic factors and the latency period of a neoplasm until its manifestation includes the factor of biological ageing. There are in humans relationships between age, localisation and incidence of tumour which can retrospectively appear as syncarcinogenic factors. Using breast carcinoma in women as an example, it is shown that a carcinogenic effect cannot be demonstrated for two of the supposed carcinogenic factors, namely repeated diagnostic radiographic measures and administration of Rauwolfia-alkaloid containing drugs.