The sequence of normal recovery of excitability in the dog heart.

The sequence with which 18 to 70 ventricular sites recovered excitability after normal excitation was determined in 15 dogs. At the epicardial level the recovery sequence was similar to that of normal activation. The sequence of excitation and recovery differed at the endocardium with some basal areas recovering excitability earlier than the apex despite later activation. Evidence of a normal epicardial to endocardial recovery sequence was also obtained. The findings are compatible with and provide a tentative explanation of some features of T waves in human body surface electrocardiograms.


Echocardiographic evaluation of posterior left ventricular wall motion in muscular dystrophy.

Maximal systolic endocardial velocity (SEVM) and maximal diastolic endocardial velocity (DEVM) were determined echocardiographically in patients with muscular dystrophy (MD). The SEVM of the muscular dystrophy patients was 5.5 +/- 0.9 cm/sec and the DEVM was 13 +/- 3 cm/sec. The SEVM in MD was significantly less than that seen in age-matched normals (P less than 0.05), persons with myotonia congenita (P less than 0.02), deconditioned patients (P less than 0.001), or older normal persons (P less than 0.05). The Sevm of the MD patients was not significantly different from persons with spinal muscular atrophy. The DEVM of the muscular dystrophy patients was significantly less (P less than 0.001-0.05) than any other group. No correlation could be found between age, heart rate, type or severity of dystrophy and SEVM or DEVM values. The echocardiogram was more selective in correctly identigying muscular dystrophy patients than the electrocardiogram. The abnormality in DEVM was present despite lack of symptoms, normal cardiovascular examination, normal chest X-ray and normal electrocardiograms in 18 of 22 patients. We believe that the DEVM correlates with myocardial relaxation.


Echocardiographic findings in atrial flutter.

Echocardiographic studies were performed in 22 patients with atrial fibrillation and atrial flutter. In atrial flutter, the echocardiograms consistently demonstrated regular undulatory waves of the posterior left atrial wall and upper left interventricular septum coinciding with each flutter wave of the electrocardiogram. The mitral valve was slightly reopened by each flutter wave occurring after diastolic mitral closure. The phonocardiogram simultaneously recorded with the echocardiogram showed only occasional atrial sounds. Coarse atrial fibrillation produced undulatory low frequency motion of both leaflets of the mitral valve during diastole. Atrial fibrillation with fine fibrillatory waves failed to show any significant and constant undulations of the left atrial wall and upper left interventricular septum. Echocardiographic evaluation of patients with atrial flutter could have diagnostic implications in doubtful cases with nondiagnostic electrocardiograms.


Diagnosis of cardiac tamponade by echocardiography: changes in mitral valve motion and ventricular dimensions, with special reference to paradoxical pulse.

The echocardiographic findings in three patients who presented with pericardial effusion and cardiac tamponade are described. Cyclic respiratory changes affected the diastolic movement of the anterior mitral leaflet, viz., during inspiration its anterior excursion decreased in amplitude and the E-F slope diminished. This inspiratory alteration in mitral valve motion was accompanied by an increase in right ventricular dimensions and a reciprocal decrease in left ventricular dimensions. Pericardial paracentesis confirmed the presence of effusion and relieved cardiac tamponade in all the patients. Repeat echocardiography, performed in two of the patients immediately after the pericardial tap, showed that the E-F slope had become steeper and that phasic respiratory variations in the diastolic motion of the anterior mitral leaflet were no longer present. The compatibility of our observations with the theories which endeavor to explain the mechanism of the paradoxical pulse in pericardial effusion with cardiac tamponade is discussed. We suggest that the abnormalities in anterior mitral leaflet motion defined by echocardiography constitute a useful addition to the study of patients with suspected cardiac tamponade resulting from pericardial effusion.


Echocardiographic diagnosis of pseudoaneurysm of the left ventricle.

The echocardiographic features of postinfarction pseudoaneurysm of the left ventricle are described for the first time. Because ultrasound allows the detection of soft-tissue structures in a manner not possible with other diagnostic techniques, the left ventricular wall can be visualized separating the left ventricular cavity from the saccular aneurysm which is delineated by pericardium and/or extracardiac tissue. In addition to these anatomic findings, relevant qualitative hemodynamic data can also be obtained. Echocardiography seems to be a safe and specific method for the diagnosis of left ventricular pseudoaneurysm. It is suggested that echocardiography should be used in the incipeint phase of pseudoaneurysm formation to detect subacute cardiac rupture.


Effects of clofibrate and sulfinpyrazone on platelet survival time in coronary artery disease.

Platelet survival time was measured (autologous labelling with 51chromium) in 68 men with coronary artery disease (CAD). Survival was shortened slightly (3.2 +/- 0.04 days; mean +/- SEM) as compared to normal (3.7 +/- 0.04 days; N = 18; P less than 0.001), and 60% had shortened survival (less than 3.3 days). Thirty-seven had hyperlipoproteinemia (36 with Type IV and one with Type III) and platelet survival was shortened (3.1 +/- 0.10 days) and significantly different from survival of men with normal lipoproteins (3.3 +/- 0,12 days; P less than 0.05). Twenty-two with shortened platelet survival and CAD received either clofibrate or sulfinpyrazone. Clofibrate prolonged platelet survival (2.6 +/- 0.09 to 3.4 +/- 0,14 days; P less than 0.001) and ten of 12 had prolongation of survival. Sulfinpyrazone increased survival (2.8 +/- 0.12 to 3.6 +/- 0.21; P less than 0.001) and nine of ten had prolognation of platelet survival. Clofibrate lowered serum cholesterol and tryglyceride but alteration in lipids did not correlate with alteration of survival. Sulfinpyrazone did not alter lipids. Data suggest that survival is shortened in CAD and that clofibrate and sulfinpyrazone alter survival. Platelet suppressant agents may prove beneficial in reducing the extent and complications of atherosclerotic arterial injury.


Pulmonary edema during volume infusion.

The relationship between left ventricular filling pressure and plasma colloid osmotic pressure to pulmonary edema was examined in a group of 37 patients, the majority of whom were hypovolemic. Sixteen patients developed pulmonary edema during fluid infusion. In the 21 patients who did not develop pulmonary edema, the left ventricular filling pressure was slightly elevated but the colloid osmotic pressure was not reduced. The majority of these patients were treated with colloid solutions (group I). In five of the 16 patients who developed pulmonary edema, the left ventricular filling pressure was elevated and there was no reduction in the plasma colloid osmotic pressure. These patients received only colloids (group II). In the other 11 patients who developed pulmonary edema, the left ventricular filling pressure was normal but the plasma colloid osmotic pressure was reduced to 16 +/- 2 torr (group III). The colloid osmotic pressure in this group was significantly less than in the other two groups (P less than 0.01). Most of these patients received large volumes of crystalloid solutions. After administration of furosemide, clearing of pulmonary edema in this group was associated with normalization of the plasma colloid osmotic pressure. Infusion of large volumes of crystalloids in hypovolemic patients can be hazardous, for reduction of the plasma colloid osmotic pressure may predispose to the development of pulmonary edema even when the left ventricular filling pressure remains normal.


Congenital absence of the left circumflex coronary artery in the systolic click syndrome.

The anatomy of the coronary artery circulation was examined by means of selective coronary arteriography in 19 patients, evaluated because of disabling chest pain and ECG abnormalities, with typical clinical findings of the systolic click syndrome (SCS). In 17 (89.5%), the elft circumflex coronary artery (LCCA) was absent; a single marginal branch arose from the left main vessel, but no vessel was present in or near the atrioventricular (A-V) groove. In contrast, the LCCA was identified in 74 of 78 control patients (94.9%) considered to have representative normal distribution of coronary artery branches, All but two patients with SCS exhibited reduced contraction of the segment of left ventricular (LV) myocardium surrounding the mitral valve ring (extent of systolic diameter decrease 1.4 +/- 3.1% vs normal 31.8 +/- 3.4%, P lwss than 0.001), as well as of the LV inflow tract (diameter decreasce 16.2 +/- 2.5% vs normal 38.6 +/- 1.8% P less than 0.001); both of these regions of the left ventricle derive their vascular supply from the LCCA, An identical segmental LV contraction disorder was observed in seven patients with functionally single vessel occlusive coronary artery disease involving the LCCA, An identical finding in this study was a relatively high incidence of absent LCCA (42%) in 19 patients with atypical angina and normal coronary arteriograms. It is concluded that a congenital anomaly of the coronary circulation, with absent LCCA, may be responsible for segmental myocardial dysfunction in some patients with SCS. In turn, this segmental contraction disorder may determine functional abnormality of the mitral valve apparatus.


Congenital heart disease in low birth weight infants.

In this study of low birth weight infants (less than 2500 g), we compared the birth weight distribution of patients with patent ductus arteriosus associated with prematurity with that of patients having congenital heart disease other than patent ductus arteriosus. Among 1436 low birth weight infants 37 infants had congenital heart disease other than patent ductus arteriosus and 198 had isolated ductus arteriosus. Infants with congenital heart disease had a mean birth weight of 2018 grams (standard deviation = 370 g) which was significantly greater than that of infants with patent ductus arteriosus. Four of the 37 infants with congenital heart disease other than ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 3.5/1000 live low birth weight infants. Seventy-eight of the 198 infants with patent ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 70/1000 live low birth weight infants. Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age and 16 were small for gestational age.


Lordotic right posterior oblique projection of the left coronary artery: a speical view for special anatomy.

The lordotic right posterior oblique projection of the left coronary artery is obtained by combining cranial angulation of the X-ray beam with rotation of the patient into the right posterior oblique position. This projection is helpful for separation of the main left coronary artery and the proximal portions of the left anterior descending and circumflex divisions, especially in patients in whom the left anterior descending artery is directed cephalad early in its course. The obtaining of an image from the lordotic right posterior oblique projection adds less than two minutes to the procedure and improves arteriographic assessment of the left coronary artery.


Alternate pathways to pulmonary venous flow in left-sided obstructive anomalies.

In cardiac anomalies causing severe obstruction in the left side of the heart, such as aortic atresia, mitral atresia, or occasionally severe aortic stenosis, maintenance of circulation depends upon shunting of pulmonary venous blood into the right atrium. The usual pathway by which the shunt is achieved is across the atrial septum through the foramen ovale. When this route is closed or severely narrowed, alternate but less common pathways may exist. These involve either anomalous connections of pulmonary veins to systemic veins or communications with the coronary venous system. In the latter, as commonly occurs in aortic atresia, left ventricular myocardial sinusoids carry pulmonary venous blood from the left ventricular cavity and into the cardiac veins. In other instances of severe left-sided obstruction, a direct communication may exist between the left atrium and the coronary sinus.


The reliability of intermittent ECG sampling in arrhythmia detection.

Although intermittent ECG sampling is a commonly used method for arrhythmia detection there are no controlled studies of its efficiency. In the present study a continuous ECG was recorded for three hours in 52 patients with ventricular tachyarrhythmias. All ECGs were interpreted minute to minute to get the true arrhythmia content. Intermittent ECG samples were simulated by analyzing the first two and first five minutes of every 15 minutes in the ECG material. Two minute long ECG samples were also used every 30 minutes. The 15 and 30 minute long periods were classified as containing arrhythmias or not according to the arrhythmia content of the samples. These findings were subsequently compared with the true arrhythmia content. The arrhythmia detection rate depends on the sampling time and true arrhythmia occurrence. The distribution of arrhythmias within the periods was also of importance. With a five minute long ECG sample about 80% of the intervals containing any type of ventricular tachyarrhythmia will be detected. This is reduced to about 50% when one minute long ECG strips are used. Infrequent types of VPCs such as R on T or ventricular tachycardia are very poorly detected also when sampling as much as one-third of the total time. The study also included a comparison between the results obtained from the clinical material and the results obtained by the use of computerized arrhythmia models. It is concluded that intermittent ECG sampling besides a low detection rate for infrequent arrhythmias and short ECG samples, also brings a risk of underestimating or overemphasizing the arrhythmia occurrence depending on a periodic type of arrhythmia distribution among the patients. These factors make intermittent ECG sampling an unsuitable method for evaluating antiarrhythmic drugs.


Electrophysiological evaluation of the Wolff-Parkinson-White syndrome: problems in assessing antegrade and retrograde conduction over the accessory pathway.

The effect of atrial pacing and recording site and ventricular pacing site on assessment of conduction over the accessory pathway (AP) was examined in a group of patients with the Wolff-Parkinson-White syndrome. The importance of initial localization of the AP by recording the sequence of retrograde atrial activation during circus movement tachycardia is demonstrated. Inability to record or pace near the AP may lead to significant errors in the assessment of the antegrade and retograde conduction properties of the AP. During ventricular pacing, retrograde atrial fusion was consistently demonstrated with laterally located APs.


Refractory periods of the accessory pathway in the Wolff-Parkinson-White syndrome.

Antegrade (AERPAP) and retrograde (RERPAP) effective refractory periods of the accessory pathway were measured at multiple cycle lengths in 47 patients with the Wolff-Parkinson-White syndrome. In 20 patients the effect of changing cycle length on AERPAP could be determined. In 12 patients Aerpap decreased by 10-45 msec, in six it increased by 10-35 msec, and in two it was unchanged. In 13 of 15 patients in whom the effect of decreasing cycle length on RERPAP could be assessed, RERPAP decreased by 10-60 msec. In eight patients, the shortest AERPAP correlated well (r equals 0.83) with the shortest R-R interval of consecutive pre-excited beats in atrial fibrillation. However, predominantly normal conduction was observed in six of 28 patients with atrial fibrillation, probably because of concealment in the bypass. Therefore, induction of atrial fibrillation during electrophysiological evaluation may privide additional information. The RERPAP at the cycle length of the arrhythmia was shorter than the cycle length of reciprocating tachycardia in all but one of 21 patients. At the same or comparable cycle lengths, AERPAP was usually greater than RERPAP.


Gradual changes of ECG waveform during and after exercise in normal subjects.

The directions and magnitudes of time-normalized P, QRS, and ST vectors, and other ECG parameters were analyzed during and after multistage exercise in 56 ostensibly healthy men aged 23 to 62. By selective averaging with a digital computer system a single representative beat was obtained from each stage. Measurements were taken from this beat. During exercise, the interval between the spatial maximum of the P wave and the onset of the QRS complex decreased while the magnitude of the P wave increased. The direction of the P vectors did not change. This pattern corresponds to the electrocardiographic manifestations of predominant right atrial overload. No significant changes in the QRS duration were observed. Also the magnitude and spatial orientation of the maximum QRS vectors remained constant. The interval between the QRS onset and the maximum spatial magnitude of the T wave shortened. The terminal QRS vectors and the ST vectors gradually shifted toward the right, and superiorly. The T magnitude lessened during exercise. In the first minute of the recovery period the P and T magnitudes markedly increased. Afterward all measurements gradually returned to the resting level. Mechanisms which may explain the observed ECG changes during and after exercise are discussed, including changes in the blood conductivity and intracardiac blood volume. Age did not contribute to the variance of the ECG measurements, but a significant reduction of this variance could be otained in some ST-segment measurements by relating them to heart rate with linear regression equations (P less than or equal to 0.05). Therefore it is expected that the sensitivity of the exercise ECG for detection of ischemic heart disease would be increased when heart rate dependent normal limits for ST-segment measurements are used. Different criteria should be employed for the interpretation of the ECG during and after exercise.


Response of patients and physicians to mass screening for coronary risk factors.

Qestionnaires were sent to 1,817 adults screened twice for coronary risk factors 10 to 11 months apart and to their physicians. Physician questionnaires returned on 1,764 persons indicated that 359 (20.4%) of the total group and 227 of 1,191 persons (19.1%) with one or more abnormal risk factors during the first screen did not return for follow-up care. Only persons with one or more risk factors were given advice or medication. When the 227 patients that did not return for follow-up are removed from the group with one or more risk factors, the 239 patients who received advice or treatment comprise 24.8% of those who could have been treated. Of the total 1,764 patients, 13.5% recieved treatment or advice. Qestionnaires returned by 1,396 persons who received follow-up care by their physicians confirmed that only those who had one or more risk factors received advice or treatment. Results of the patient questionnaires show that 223 persons received advice or treatment (23.2% of all with risk factors who returned for follow-up; 16.0% of the 1,396 persons). Furthermore, of 116 persons prescribed medication for risk factor control, 60 (51.7%) were not taking this medication. Of 20, persons given advice for reduction of risk factors, 162 (78.9%) were not following this advice. These data indicate physician indifference and patient apathy to reduction of coronary risk factors in asymptomatic individuals.


Right ventricular performance in patients with coronary artery disease.

While left ventricular (LV) performance in patients with coronary artery disease (CAD) has been extensively investigated, little attention has been given to right ventricular (RV) function in this disease. For this purpose, a new geometric model for RV volume has been developed and RV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI) and ejection fraction (EF) have been determined from biplane RV cineangiograms in 26 patients. Eight patients served as normal (control) subjects (group I). Eighteen patients with obstructive CAD comprised two other groups: six who had no significant disease of the right coronary artery (RCA) (group II) and 12 who had a high grade RCA lesion (group III). The mean values for EDVI, SVI and EF in group I were 76 +/- 11 ml/m2, 50 +/- 6 ml/m2, and 66 +/- 6%. The only significant difference between groups I and II was that SVI was lower in group II than in group I (P less than 0.01). No measurements in groups II and III were statistically different from each other. However, markedly subnormal values were found in group III (EDVI: 61 +/- 16 ml/m2, SVI: 33 +/- ml/m2 and ef: 52 +/- 7%); all values being significantly lower (SVI and EF: P less than 0.001; EDVI: P less than 0.05) than in group I. RV end-diastolic pressure was normal in all patients. These findings may related to 1) reduced RV compliance, 2) distorted LV geometry, 31 possible RV ischemia or 4) reduced Frank-Starling effect.


Five year follow-up of double Master's test, maximal treadmill stress test, and resting and postexercise apexcardiogram in asymptomatic persons.

The double Master's test, the maximal treadmill stress test, the resting apexcardiogram, and the postexercise apexcardiogram significantly correlated with the development of subsequent coronary heart disease within five years in 100 asymptomatic persons. The maximal treadmill stress test correlated better than the double Master's test in predicting subsequent coronary heart disease. The presence of both an abnormal maximal treadmill stress and an abnormal a-wave ratio in the postexercise apexcardiogram had  the best value in predicting subsequent coronary heart disease.


Noninvasive detection of regional myocardial ischemia using rubidium-81 and the scintillation camera: comparison with stress electrocardiography in patients with arteriographically documented coronary stenosis.

The sensitivity of rest and stress myocardial perfusion studies using scintillation camera imaging of intravenously administered rubidium-81 (81Rb) in the detection of myocardial ischemia was compared to that of stress electrocardiography by relating results in 40 patients to the degree of stenosis delineated by coronary arteriography. Of 33 patients with greater than 75% stenosis of at least one of the three major coronary vessels (significant stenosis), rest and stress 81Rb imaging detected ventricular ischemia in 29 (88%) whereas simultaneous stress electrocardiography was positive (1 mm or greater horizontal ST-segment depression) in only 19 (58%) of the same patients. Five of the 29 patients who developed stress-induced scintigraphic evidence of ischemia did not develop angina or a positive electrocardiogram with stress. In 31 of the 33 patients with significant coronary stenosis, either the stress scintigram or the stress electrocardiogram  was positive. In seven patients with less than 50% narrowing of a major coronary vessel on coronary arteriography, the stress scinitigrams were negative, whereas the stress electrocardiograms were positive in the two of these patients with the syndrome of angina with normal coronary arteriograms. It is concluded that high resolution images of the myocardium can be obtained with 81Rb using the scintillation camera with special shielding, and that rest and stress 81Rb scintigraphy appears to provide greater sensitivity and specificity when compared to stress electrocardiography in the nininvasive identification of significant coronary stenosis.


Use of atropine in patients with acute myocardial infarction and sinus bradycardia.

Fifty-six patients with acute myocardial infarction complicated by sinus bradycardia (SB) were treated with intravenous atropine and monitored in a coronary care unit. Atropine decreased or completely abolished premature ventricular contractions (PVCs) and/or bouts of accelerated idioventricular rhythm in 27 of 31 patients (87%) and brought systemic blood pressure up to normal in 15 of 17 patients (88%) with hypotension. In addition, atropine administration was associated with improved atrioventricular conduction in 11 of 13 patients (85%) with acute  inferior myocardial infarction associated with 2 degrees or 3 degrees atrioventricular block. Seven patients developed ten significant adverse effects: ventricular tachycardia or fibrillation in three, sustainedsinus tachycardia in three, increased PVCs in three, and toxic psychosis in one. These major adverse effects correlated with either a higher initial dose of atropine (i.e., 1.0 mg aa compared with the usual 0.5 or 0.6 mg) or a total cumulative dose exceeding 2.5 mg over 21/2 hours. Atropine is the drug of choice for management of patients with SB and hypotension and is effective in the treatment of ventricular arrhythmias as well as conduction disturbances in patients with inferior myocardial infarction. Serious adverse effects, however, preclude use of atropine without careful medical supervision.


Relationship between echocardiography, cardiac output, and abnormally contracting segments in patients with ischemic heart disease.

Twenty-four patients with proven coronary artery disease and abnormally-contracting segments were studied by both echocardiography and biplane angiographic techniques. Comparison was made between the left ventricular biplane angiographic volumes and those obtained from echocardiographic measurements which were calculated from cubed function and regression equaltion methods. The percent abnormally contracting segment (ACS) was obtained from biplane left ventricular angiography and was calculated from the diastolic and systolic anteroposterior and lateral angiocardiograms. The angiographic end-diastolic volume correlated with that calculated from the echocardiographic dimensions with an r value of 0.865 and SEE of +/- 22.64 ml. The angiographic end-systolic volume and echo end-systolic volume did not correlate as well, with an r = 0.7063. The difference in stroke volume predicted by the diastolic and systolic echocardiographic dimensions and the actual stroke volume determined by Fick technique was related to the percent abnormally contracting segment of the left ventricle (r = 0.8967). The percent ACS could be estimated from echo and Fick stroke volume measurements by the cube function and regression equations. Echo ventricular volume determinations were analyzed for the cube function method and the regression equations of Fortuin et al. and Teichholz and coworkers, with the method of Fortuin et al. producing the most sensitive relationship: % ACS = 0.32 (SVecho - SVFick) % + 8.9%. The correlation coefficient for the estimate was 0.8967 with a SEE of +/- 4.78%. In patients with coronary artery disease and abnormally contracting segments, echocardiography can provide reliable measurements of left ventricular end-diastolic volume but estimates of end-systolic volume are less accurate. If mitral regurgitation or a ventricular aneurysm can be excluded, the difference in echocardiographic and forward stroke volume by an independent method is related to the angiographic and forward stroke volume by an independent method is related to the angiographic abnormally contracting segment, and this relationship permits estimation of the size of the abnormally, contracting segment.


The echocardiographic assessment of pulmonary artery pressure and pulmonary vascular resistance.

Serial assessment of the status of the pulmonary vascular bed requires bed requires cardiac catheterization. We have demonstrated the right ventricular systolic time intervals (RVSTI) may be measured from the pulmonary valve echo. The right ventricular ejection time (RVET) and right pre-ejection period (RPEP) were measured in 45 normal patients. The RVET and RPEP decreased with increasing heart rate but increased with age. The RPEP/RVET, however, was uninfluenced by either age or heart rate. The RPEP/RVET was, therefore, determined from the pulmonary valve echo in 64 patients with congenital heart disease who underwent cardiac catheterization. Increased pulmonary artery diastolic pressure (PADP), pulmonary vascular resistance (PADP), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) resulted inan increased RPEP/RVET. The use of the RPEP/RVET permitted the serial echographic evaluation of the pulmonary vascular bed in selected patients; marked elevation of the ratio indicated the presence of pulmonary hypertension.


Aortic root dilatation and mitral valve prolapse in Marfan's syndrome: an ECHOCARDIOgraphic study.

Echocardiographic and phonocardiographic findings in 35 patients with Marfan's Syndrome and ten patients without Marfan's or other clinically apparent connective tissue disorders but with angiographic and echocardiographic evidence of mitral prolapse are reported and compared. Echocardiography revealed aortic root dilatation and/or mitral valve prolapse in 97% of the patients with Marfan's Syndrome. Aortic root dilatation was found in 60% of this group (74% of males, 33% of females) while mitral valve prolapse was found in 91% (87% of males, 100% of females). The incidence of aortic dilatation and mitral prolapse in patients with Marfan's syndrome was essentially equal in children and adults of the same sex. None of the nine adults or one child with mitral prolapse but without evidence of Marfan's Syndrome or other clinically apparent connective tissue disorder had aortic root enlargement. Ausculatory examination and phnocardiography revealed abnormalities in 54% of the patients with Marfan's Syndrome. Aortic regurgitation was found in 23% of this group (35% of males, 0% of females) while mitral regurgitation and/or mitral clicks were found in 46% (39% of males, 58% of females). Aortic regurgitation was much more frequent in adult males with Marfan's Syndrome (7/14, 50%) than male children (1/9, 11%), while the incidence of abnormal mitral sounds was essentially the same in adults (33% of males, 60% of females) and children (43% of males, 57% of females) of the same sex with Marfan's Syndrome. Abnormal mitral sounds were more frequent in patients without Marfan's who had mitral prolapse (90%) than in those with Marfan's (46%). It appears that cardiac abnormalities are a consistent manifestation of Marfan's Syndrome and that ultrasound is a more sensitive indicator of these abnormalities in such patients than ausculation or phonocardiography.


The variable echocardiographic features in aortic valve endocarditis.

The echocardiographic abnormalities in five cases of aortic valve endocarditis are described and are correlated with the anatomical appearance of the valve at the time of aortic valve replacement. These electrocardiographic findings are compared with those which have been reported previously in this condition. Thickening of the aortic leaflets in systole or multiple linear or coalescent aortic valve echoes in diastole are highly suggestive of valvular vegetations. Ruptured aortic leaflets may produce chaotic, high-frequency echo patterns which differ from those produced by vegetations. The specificity of these echocardiographic patterns is discussed.


A reassessment of the echocardiogram in mitral stenosis.

Echocardiographic and cardiac catheterization findings were compared in 61 patients with mitral stenosis without other significant lesions in an attempt to determine the clinical usefulness of echocardiography in the assessment of such patients. There was a poor correlation between the E-F slope on the echocardiogram and the calculated mitral valve area (r = 0.51). A review of reported data relating the E-F slope to mitral valve area indicated that echocardiographic assessment of mitral valve area had low sensitivity and specificity. The amplitude of excursion of the anterior leaflet did not differ significantly in patients undergoing valvotomy and those undergoind valve replacement. The data obtained suggest that while the echocardiogram is a reliable method of diagnosing mitral stenosis, the E-F slope is an unreliable index of the severity of the lesion.


Identification of congenital malformations of the great arteries in infants by real-time two-dimensional echocardiography.

Real-time, two dimensional echocardiography was used to identify great artery relations in 23 infants and small children, including 16 patients with angiography documented transposition of the great arteries, tetralogy of Fallot, or pulmonary aresia. Using this technique, the heart was scanned perpendicular to its long axis at the origin of the great arteries. Great arteries cross-sectioned perpendicular to their long axes appear as circles; when sectioned longitudinally these arteries appeared as elongated sausage-shaped structures. I- patients with normally related great arteries, a curcular structure (aorta) always was positioned posterior to an elongated, sausage-shaped structure (distal right ventricular outflow tract and proximal main pulmonary artery). In transposition of the great arteries, two adjacent circular structures were observed; the anterior circle (aorta) was located to the right, left or directly anterior to the posterior circle (pulmonary artery). In pulmonary atresia or hypoplasis, a large posterior circle (aorta) was associated with an anteriorly positioned structure that was either short and small (atretic right ventricular outflow tract) or elongated with an area of severe narrowing (hypoplastic right ventricular outflow tract). Thus, real-time two-dimensional echocardiography provides a rapid, noninvasive means of accurately identifying congenital malformations of the great arteries in infants and small children and may be a useful adjunct to cardiac catheterization in the diagnosis of cyanotic congenital heart disease.


Abnormalities of right ventricular function following Mustard's operation for transposition of the great arteries.

Postoperative data were obtained at cardiac catheterization in twelve patients studied 6-29 months following Mustard's operation for transposition of the great arteries (TGA) to assess the incidence and severity of abnormalities of right ventricular (RV) function. Age at operation was 5-13 months in seven patients (infant group) and 19-25 months in the remaining five patients. RV end-diastolic volume (EDV) decreased in all patients following surgery and averaged 123% of normal in the postoperative group (NS). RV ejection fraction (EF) was depressed postoperatively averaging 0.45 (69% of normal (P less than 0.001) as was RV systolic output (78% of normal, P less than 0.01). LVEDV averaged 65% of normal (P less than 0.001), LVEF 0.67 (103% of normal, NS), and LV systolic output 67% of normal (P less than 0.001) following operation. Left atrial (systemic venous) volume was decreased in all postoperative patients averaging only 39% of normal (P less than 0.001). A high incidence (greater than 50%) of partial baffle obstruction was found and LV systolic output showed a significant negative correlation with baffle gradients. The low output postoperatively may be related to decreased LV filling pressure, a small LV reservoir, and thus a small atrial "booster pump." Pressure-velocity indices of RV contractile function in four patients showed a poor correlation with pump function. Long-term follow-up will be required to determine the clinical significance of the abnormalities of venous return and ventricular function.


Surgical palliation of tricuspid atresia.

In the 20-year period ending December 31, 1973 we operated on 105 patients for palliation of tricuspid atresia (TA) with reduced pulmonary blood flow. Pott's anastomosis (85), Blalock-Taussig anastomosis (19), intrapericardial aorta (Ao)-to-right pulmonary artery (RPA) (18), Glenn procedure (3) and miscellaneous shunts (2) have been used. Of patients undergoing operation more than 15 years ago, 45% (9/20) are still alive. The over-all operative mortality was 9%. It was highest in patients less than one month of age (7/23, 30%). There were no operative deaths in patients older than 12 months. The median age at first operation for the entire series was five months. Our results indicate the Pott's anastomosis and Ao-to-RPA anastomosis are superior to the Blalock-Taussig anastomosis (BT) for palliation of TA. Of patients surviving BT, 69% (11/16) required reoperation, compared to 22% (17/78) surviving Pott's anastomosis and 13% (2/16) surviving Ao-to-RPA shunts. All three patients undergoing Glenn procedures (superior vena cava-to-RPA anastomosis) required reoperation or died without significant benefit. Ballon atrial septosomy and Pott's anastomosis appear to be indicated for infants less than six months of age, and Ao-to-RPA shunt with simultaneous atrial septectomy (if indicated) for older children.


Unexpected cardiac arrest in patients after surgical correction of tetralogy of Fallot.

Four of 220 patients without bifasicular block (complete right bundle branch block and left anterior hemiblock) or transient complete heart block immediately after surgery had an unexpected cardiac arrest one to 15 years after satisfactory surgical repair of tetralogy of Fallot. The postoperative electrocardiograms (ECG) revealed complete right bundle branch block in two patients and no intraventricle conduction abnormality in two patients. Each of the four patients had premature ventricular contractions on previous postoperative ECG. The cardiac arrest occurred during normal activity in three patients and mild exercise in one. Following the cardiac arrest, three patients died and one patient survived. Eighteen months before the cardiac arrest, the survivor had a stress test which revealed multifocal premature ventricular contractions with short bursts of ventricular tachycardia after exercise. This ventricular arrhythmia was suppressed with quinidine therapy. Although complete heart block cannot be excluded in these four patients, we reasoned that the cardiac arrests were probably preceded by ventricular tachyarrhythmia. Because of this experience, we believe that any patient who has had intraventricular surgery should be evaluated for ventricular arrhythmia. If frequent premature ventricular contractions or serious ventricular arrhythmias are documented, we seriously consider antiarrhythmic therapy in an attempt to prevent ventricular tachyarrhythmias and sudden death.


Aortic sinus of Valsalva aneurysms simulating primary right-sided valvular heart disease.

While acute regurgitation is the most common valvular lesion associated with aortic sinus of Valsalva aneurysms, this report describes the pathological findings in five patients in whom primary right-sided valve dysfunction was simulated by sinus of Valsalva aneurysms. In two patients aneurysms of the noncoronary sinus projected into the right atrium at the level of the tricuspid valve and caused tricuspid incomptence. In three patients aneurysms of the right sinus of Valsalva projected into the right ventricle immediately below the pulmonic valve and caused pulmonary outflow tract obstruction. In only one of these patients was the aneurysm perforated at necropsy. Although valvular dysfunction was evident clinically, in none was there a clinical suspicion of a sinus of Valsalva aneurysm. In addition to valvular dysfunction, two patients had conduction disturbances and two, right coronary arterial occlusions found to be the result of aneurysms. The risks of valve dysfunction, arrythmias, aneurysm rupture, and sudden death and the ability to correct this lesion surgically make it especially important to consider aortic sinus of Valsalva aneurysm as a cause of obscure right-sided valvular disease.


Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.

Thirteen patients with severe hypertension were treated with combined minoxidil, propranolol, and furosemide (mean daily doses 33 mg, 475 mg, and 578 mg, respectively) for nine to twenty-five months (mean 13.8). Average mean blood pressure while on aggressive therapy with conventional medication was 144 +/- 14 mm Hg; on minoxidil and propranolol it was 108 "/- 10 mm Hg (P less thator to optimum blood pressure control and required large doses of furosemide to control. Propranolol blunted the reflex tachycardia associated with arteriolar dilator therapy but all patients continued with a clinically hyperdynamic circulation. Seven of seven had elevated ejection fractions on echocardiogram, and two of three had elevated cardiac indices. Three of three who had heart catheterization had pulmonary hypertension which was aggravated by exercise. An additional three patients on hydralazine, propranolol, and furosemide also had pulmonary hypertension suggesting this is not unique to minoxidil. Two of thirteen developed pericardial effusions. Renal function improved in three and worsened in three.


Left atrial appendage aneurysm: correlation of noninvasive with clinical and surgical findings: report of a case.

Congenital left atrial appendage aneurysm is rarely diagnosed on the basis of an abnormal cardiac silhouette. Patients with a left atrial appendage aneurysm often present with symptoms of systemic emboli or supraventricular arrhythmias. A patient with left atrial appendage aneurysm was diagnosed by correlation of two noninvasive techniques echocardiography and radionuclide scintiscanning. Angiography was confirmatory and aneurysmectomy was successfully performed.


Comparison of 3-kit methods for determination of human chorionic somatomammotropin by radioimmunoassay.

1. Three commercially available kit procedures for human chorionic somatomammotropin (HCS) were investigated. 2. The comparison of the methods included procedure, accuracy, precision, sample requirement and time required for analyses. 3. While one kit gave significantly higher values and requires more time to obtain results, each of 3 procedures was concluded to provide clinically useful information.


Variations in ovarian steroid levels during the luteal phase of the menstrual cycle.

1. Six subjects were investigated during the luteal phase of the menstrual cycle to determine whether the ovarian steroids, estrogen and progesterone were released in an episodic manner. 2. Analysis of plasma obtained every 20 min. during a normal working day provided no evidence for pulsatile release of either steroid although values were lower in the afternoon than in the morning (p less than 0.001). A good correlation (r=0.908) was obtained for the release of both hormones. 3. Cortisol secretion was inversely related to that of the ovarian steroids.


Enzymatic endpoint analysis of glucose with the hexokinase method and the Union Carbide fast centrifugal analyzer.

1. We describe an enzymatic endpoint method for glucose using the hexokinase reaction and the Union Carbide fast centrifugal analyzer. The new method permits the direct spectrophotometric measurement of serum blanks, and eliminates the need for separate blank determinations or computer-assisted calculation of the sample blank absorbance values. 2. The direct automatic blanking is accomplished by measuring the absorbance of the test solution 2 seconds after the reactants have been mixed. Our studies show that no appreciable conversion of glucose occurs during this time interval. 3. The results of the new method agree well with the results from the conventional hexokinase assay. In addition, the method requires only 5 microliters of serum, and has a high sample throughput rate.


Identification of a creatine kinase inhibitor in human serum.

Human skeletal muscle creatine kinase is inhibited by a dialyzable factor in human serum. The inhibitor was fractionated from other serum components by ultrafiltration and chromatography on Sephadex G-10 and was identified as uric acid by spectral, chromatographic, and kinetic methods. Its quantitative kinetic properties are identical to those of uric acid, both as a substrate for uricase and as an inhibitor of creatine kinase. Inhibition of creatine kinase by the natural inhibitor and by known uric acid is completely reversible by addition of thiol compounds.


The albumin binding of unconjugated bilirubin in serum.

1. The limited bilirubin binding capacity of human serum albumin, and the fact that kernicterus can occur once the serum unconjugated bilirubin concentration exceeds this capacity, makes the assessment of non-albumin bound free bilirubin valuable in cases of severe neonatal hyperbilirubinemia. 2. Present methodology for this assessment utilizes Sephadex column chromatography, and is somewhat tedious and slow. 3. We have developed a procedure for assessing the albumin binding capacity of serum by titrating a sample of the serum with T-20 Dextran coated charcoal. 4. The method requires 2 ml of serum, takes 90 minutes to complete and is highly reproducible. 5. By this method, we can determine the reported secondary loose binding capacity of the albumin as well as the tight binding capacity which is determined by existing methods. 6. The tight binding capacity of a pool of normal adult human serum was found to be 20 mg/dl of serum. 7. This is in agreement with existing methods. The loose binding capacity was found to be an additional 10 mg/dl of serum. Added phenobarbital was found to lower the tight binding capacity, but not the secondary capacity.


A gas-liquid chromatographic determination of p-chlorophenoxyisobutyric acid and its comparison to an ultra violet method.

1. A gas-liquid chromatographic procedure for the determination of p-chlorophenoxyisobutyric acid (CPIB) has been elaborated and compared to the UV spectrophotometric procedure of Barrett and Thorp. 2. Both methods are specific when used to determine CPIB levels in normal sera from laboratory animals or humans treated with clofibrate (Atromid-S). Serum from patients treated with other drugs or abnormal sera from patients affected with a variety of diseases will often contain high and fluctuating levels of non-specific UV absorbing substances and this usually precludes the use of the UV procedure. 3. The GLC method is also applicable to the analysis of CPIB in urine samples.


Improved direct colorimetric method for the determination of total serum globulins.

1. A direct, fast, and efficient manual method is described for determining total serum globulins. The procedure is based on the reaction of tryptophan residues with glyoxylic acid in the presence of an oxidizing agent to produce a highly colored 4-carboline derivative. 2. A single, odorless reagent is employed and Beer's law is obeyed up to at least 7 g/100 ml of globulin at 565 nm. 3. Results of parallel assays demonstrate good agreement between our method and a reference cellulose acetate electrophoretic method and poor agreement with a HABA dye binding method.


The measurement of Rivotril in whole blood by gas liquid chromatography.

Rivotril is extracted from blood into an organic solvent mixture, Mogadon, (Nitrazepam) is used as internal standard. The drugs are then back-extracted into acid which is heated to produce the corresponding benzophenones. These are extracted into benzene and separated by gas liquid chromatography with electron capture detection.


Quality assurance in health care: missions, goals, activities.

The most challenging mission of medical personnel today is quality assurance in health care. To meet this challenge, the essential elements of a six-phase system for total quality control for the medical laboratory are outlined under the headings of design control, incoming material control, process control, output control, reliability control, and special verification studies. Review of existing goals and activities of programs related to this mission indicates both problems and rich opportunities for individual laboratory professionals and their organizations. For effective implementation of this mission, the laboratory professionals will have to create the atmosphere of a collegium where all interested scientists communicate across disciplines to eliminate the systematic biases and improve the accuracy, precision, and specificity of clinical laboratory measuring systems, to assure medically meaningful and useful assay results for the broad spectrum of health care that is necessary for the well, the near-well, and the sick.


Concepts for the rational selection of assays to be used in monitoring therapeutic drugs.

As the domain of monitoring therapeutic drugs rapidly expands from experimental investigations to everyday patient care, all clinical laboratory scientists, but especially clinical chemists, must learn to deal with their involvement in this expansion. First, the theoretical concepts underlying clinical pharmacology must be appreciated so that the laboratory's participation in it can succeed. Individual differences cause unpredictable variations of response to the customarily standardized drug dosage. Properly used, assays of drugs in blood can eliminate such variabilities. Second, the practical selection of which drug assays a laboratory intends to provide must be based on a rational evaluation of assay usefulness, integrating both clinical and laboratory considerations. Such a decision model is suggested; it is generally applicable in allocating priorities among an ever-increasing number of proposed tests under the constraint of finite resources.


Kinetic determination of glucose with the GEMSAEC (ENI) centrifugal analyzer by the glucose dehydrogenase reaction, and comparison with two commonly used procedures.

A new glucose dehydrogenase preparation has been used to determine the glucose concentration in serum or plasma with the GEMSAEC(ENI) analyzer. The reaction is sufficiently linear to be suitable for a kinetic determination. A sample volume of 15 mul or less is needed, and 14 determinations can be done simultaneously within 160 s (the time needed for loading the samples and reagents into the distribution disc plus a reaction time of 70 s). The reaction is linear up to 300 mg of glucose per 100 ml, but with special computer software linearity could be extended to 1 g of glucose per 100 ml. Day-to-day and within-day precision have been tested with a number of different sera and standards. Accuracy has been checked by comparing the results with those obtained by the hexokinase and the glucose oxidase/peroxidase methods. A better agreement was found with the hexokinase method. The proposed procedure has the advantage of involving only one enzymatic step and of directly measuring reduced coenzyme formation at 340 nm.


Simultaneous detection of morphine and barbiturates in urine by radioimmunoassay.

This report describes a radioimmunoassay for the simultaneous detection of morphine and barbiturates. Morphine and barbiturate antibodies, obtained from goats, were mixed with 125l-labeled antigens. By adjusting concentrations of the morphine and barbiturate antibodies and radiolabeled antigens, closely superimposed standard curves for the two drugs would be obtained. As a consequence, similar response curves were obtained for urine specimens containing morphine or barbiturates. Although concentrations as low as 25 mug/liter could be measured, to ensure against false positive reactions the test should be performed at the 100 mug/liter concentration. Unknown samples positive by the dual assay were confirmed by separately testing the specimens with the individual radioimmunoassay specific for morphine or barbiturate. Equivalency tests of urines positive for morphine, positive for barbiturates, or negative for both demonstrated complete correlation between the single and dual assays. The mixed reagent retained its sensitivity and specificity for at least three months when stored at 4 or 25 degrees C. The dual radioimmunoassay is a rapid, simple procedure that can be adapted to automated processes and that is suitable for large- and small-scale screening.


Thyroid-function tests in diphenylhydantoin-treated patients.

We compared the free-thyroxine index in normal adults and in euthyroid patients taking diphenylhydantoin. All subjects had normal serum thyrotropin concentrations. Serum thyroxine concentrations were determined by two commonly used competitive protein-binding assays, which yielded slightly different values, but which consistently showed the same degree of decrease in mean serum thyoxine concentration in drug-treated patients as compared to the normal subjects. When 14C-labeled diphenylhydantoin was added to serum before the assay, it was separated from thyroxine in the Ames method, whereas by the Murphy-Pattee method both drug and thyroxine were extracted together. Thus, the decrease in serum thyroxine concentrations during diphenylhydantoin therapy cannot be the result of drug interference with the binding of thyroxine to binding proteins in the assays. Triiodothyronine uptake, evaluated by two methods, was identical in the two groups. The free-thyroxine indexes for all normal persons were within the manufacturer's normal range, but 21% of the drug-treated patients had subnormal indexes by the Ames method; the indexes as measured by the Murphy Pattee method were in the lower half of the normal range. Because the triiodothyronine uptake was unaffected by the drug treatment, the decreases in the indexes must have resulted from the lower serum thyroxine concentrations. We conclude that the free-thyroxine index may not provide a valid estimate of either the clinical status or the free-thyroxine concentration in patients taking diphenylhydantoin.


Influence of age, sex, and oral contraceptives on human blood cholinesterase activity.

We estimated cholinesterase (EC 3.1.1.8) activities in erthrocytes and plasma of 443 men, 188 women not taking oral contraceptives, and 70 women who were taking oral contraceptives. Men in the first six decades of life had higher plasma cholinesterase activity than did women who were not taking oral contraceptives, and these women had higher plasma cholinesterase activity than women taking oral contraceptives. After the age of 60 there was no intersex difference. Activity of erythrocytes from the oral contraceptive group was higher than in the other groups, men had the lowest activity, and there was an increased activity with age in both sexes until the age of 60. These findings suggest that there is no single "normal" value for cholinesterase activity for adults.


Trend detection in control data: optimization and interpretation of Trigg's technique for trend analysis.

A method for trend detection, Trigg's technique [Oper. Res. Q. 15, 271 (1964)], has been investigated for use in monitoring trends in control data produced by multitest continuous-flow analyzers. Simulated trend data were used to optimize the method. Actual control data were analyzed retrospectively to determine the frequency of trends and the accuracy of several parameters obtained from Trigg's method. The prospective use of the technique has successfully uncovered important trends. Criteria for the interpretation of the Trigg's trend data are suggested and an algorithm for the computer implementation of Trigg's calculations is included.


Erythrocyte 2,3-diphosphoglycerate as related to diabetes and obesity.

2,3-Diphosphoglycerate was determined in the erythrocytes of 17 diabetic and 18 obese patients. Results for obese subjects were significantly (P less than .01) different from those obtained for 21 healthy subjects. Results for obese and diabetic patients also differed significantly (P less than .01) but not those for diabetic and healthy subjects. Hemoglobin, hematocrit, or bicarbonate measurements did not differ among the three groups.


Kinetic enzymatic method for determining serum creatinine.

Creatinine amidohydrolase is used to measure serum creatinine in a totally enzymatic procedure. Creatine, produced by hydrolysis, is acted upon by creatine kinase, and then by pyruvate kinase and lactate dehydrogenase, to result in a change in absorbance at 340 nm. The amount of creatinine present is related to the rate of change in A340 and is determined from a standard curve. Absorbance and concentration are linearly related to 100 mg/liter and only 250 mul of serum is required. At 1.0 g/liter, heparin, oxalate, citrate, ethylenediaminetetraacetate, ascorbate, or glucose had no significant effect on the accurate determination of creatinine; higher concentrations (30 g/liter) had inhibitory effects on the test. Analytical recovery of creatinine added to either normal or abnormal sera averaged 102%. When results of this procedure and of the standard direct Jaffé test were compared, the latter were significantly higher. Unlike the Jaffé method, the present method of determining creatinine is rapid (about 10 min per test), subject to few or no interfering substances, and requires no serum deproteinization.


Colorimetric, enzymatic, and liquid-chromatographic methods for serum uric acid compared.

We describe high-performance liquid chromatography in conjunction with electrochemical detection as a possible reference method for serum uric acid. Separation was effected on a column packed with "Vydac" strong anion-exchange resin, with use of a detection potential of +0.80 V vs. an Ag/AgCl reference electrode. Results were linearly related to concentration up to 1.0 g/liter, and no interferences were seen. Assay of human sera gave within-run and day-to-day coefficients of variation of 0.83% and 1.1%, respectively; analytical recoveries averaged 100%. Comparison of the new procedure (x) with the phosphotungstate and uricase methods (y) showed the following linear regression and correlation coefficients for results: y equal 0.963x + 0.219 (r = 0.995), and y = 0.991x + 0.165 (r = 0.999), respectively. As compared to these methods, the procedure we describe is more accurate, because of the selective detection system based on retention time and redox potential. Samples can be analyzed at the rate of 20/h. No deproteinization is required.


Quantitative method for estimating fecal amino acids.

We describe a method for quantitatively estimating 24 ninhydrin-reacting substances, including the commoner amino acids, in fecal dialysate prepared from ingested dialysis bags retrieved from fresh stool. It is accurate to 2 mumol of alpha-amino nitrogen per liter of fecal dialysate, and for most substances recovery of added standards is 100%. It involves dilution, ultrafiltration, and automated ion-exchange column chromatography of the dialysate. Some normal values are provided.


Critical assessment of phospholipid measurement in amniotic fluid.

We assessed several methods of inorganic phosphate assay for their suitability in estimating phospholipids in digested extracts of amniotic fluids. The extraction and digestion procedures used for phospholipids from amniotic fluid were also examined critically. The effect of contamination by blood or obstetric cream has been examined. Accordingly, we suggest a method for measuring total phospholipids in amniotic fluids, and results of it are compared with the lecithin/sphingomyelin ratio measurement in some clinical situations.


Otimum kinetic enzymatic procedures for glucose and triglycerides in plasma and serum.

I describe optimum kinetic procedures for measuring glucose and triglycerides in plasma and serum by enzymatic techniques. Glucose was measured by the hexokinase method at a 1000-fold sample dilution. Absorbance and concentration are linearly related for concentrations up to 4 g/liter. Results are reproducible to about 25 mg/liter (standard error). Comparisons between the kinetic glucose method described here and an automated o-toluidine and a manual end-point method showed no apparent bias between the methods; correlation coefficients were 0.998 and 0.991, respectively. Triglycerides (triacylglycerols) were measured in a fully enzymatic system by measuring free glycerol after hydrolysis with lipase. Absorbance and concentration are linearly related to greater than 2.5 g/liter at a 300-fold sample dilution. Repeatability was about 30 mg/liter (standard error). Compared with a manual method, the correlation coefficient was 0.978, with a slope of 0.93.


Modification of the Fiske and SubbaRow method for total phospholipid in serum.

Many of the difficulties encountered in the original Fiske and SubbaRow method for estimating serum phospholid were corrected through the use of vanadium pentoxide, a catalyst used in sample digestion, and through other minor modifications. Results obtained by the modified method agree well with those obtained by three other established phospholipid procedures. The greatly improved speed, simplicity, accuracy, and precision now makes the modified Fiske and SubbaRos method ideal for clinical or research use.


Some theory of reference values. I. Stratified (categorized) normal ranges and a method for following an individual's clinical laboratory values.

The conventional population-based normal range has recently been shown to be a generally defective reference criterion for assessing individual laboratory test results. Applying a previously derived formula to published data, we find that the use of age-, sex-specific normal ranges may fail to produce a substantial improvement in sensitivity over nonspecific ranges, even when age-sex differences in mean values are statistically significant. This occurs when the difference in means is not accompanied by a sufficient reduction in the variation among individuals within a given class. Turning therefore to comparison of an individual's current measurement with his own previous value(s), I suggest a simple statistical model that leads to sequential testing of each new observation against an exponentially weighted moving average of previous results. Estimates of biological and analytical components of variance are required. The ability of this method to detect trends in very short series is explored with the aid of computer-simulated laboratory data. A sample of these data is also used to illustrate the application of these estimation and testing procedures by means of a graph.


Automated immunochemical method for determination of urinary protein of plasma origin.

An automated continuous-flow procedure has been developed for the rapid determination of urinary proteins of plasma origin. Antiserum to whole human plasma was used as the reagent, and the antigen-antibody reactions were quantitated by nephelometry. By adding polyethylene glycol (mol wt 6000-7500) to the reaction medium, reaction time was decreased to less than 3 min; no sample blanks were required; and samples were analyzed at a rate of 70 per hour. Recovery studies yielded an average of 98.5% of the added protein. In-run replicate precision (CV) of the method was 1.45%; day-to-day precision was 2.58%.


Simplified photometric copper-soap method for rapid assay of serum lipase activity.

We modified the method of Yang and Biggs [Clin. Chem. 17, 512 (1971)] for greater speed and simplicity. Serum is incubated with an emulsified olive oil substrate, the fatty acids extracted, the copper soap formed, and phases separated, all in a single tube. An aliquot of the organic phase is removed for color development. One analysis can be completed in 35 min, 20 in less than 2 h. The method is accurate and precise. Results correlate well with the unmodified colorimetric method, and with the classical titrimetric lipase procedure. The reference interval (normal range) is 20 to 180 U/liter.


Rapid, specific assay for plasma cortisol by competitive protein binding.

We describe a modified competitive protein-binding method for assay of plasma cortisol. Plasma samples are deproteinized by dilution with an ethanol/phosphate buffer, followed by heating at 100 degrees C for 2 min. Horse serum is used as the source of transcortin. Free radioactivity is separated from the protein-bound component by partition into liquid scintillation counting within 60 min. The assay has better specificity and precision than a competitive protein-binding assay in which ethanol extraction and Florisil adsorbent are used, and results correlate well with those of a specific radioimmunoassay method.


Fluorometric serum lipase assay: evaluation of monodecanoyl fluorescein as substrate.

The elements of the mechanized fluorometric lipase (EC 3.1.1.3) assay of Fleisher and Schwartz [Clin. Chem. 17, 417 (1971)] were made optimum; a manual adaptation was also developed. Hydrolysis of the monodecanoyl fluorescein substrate by hog pancreatic lipase is a zero-order reaction. The hydrolytic activity of normal human serum, serum from hospitalized patients without pancreatitis, and serum from patients with acute pancreatitis showed considerable overlap. Bile salts, considered activators in titrimetric or turbidimetric lipase assays, inhibited hydrolysis of the substrate by human serum. We conclude that monodecanoyl fluorescein is not a specific substrate for the serum lipase measured in acute pancreatitis.


Gas chromatographic/thin-layer chromatographic analysis of acetylated codeine and morphine in urine.

This procedure positively identifies codeine and morphine in urine. Urine samples are hydrolyzed and extracted with organic solvent, and the extracts are evaporated and acetylated. The presence of codeine and morphine is ascertained by gas chromatography (3% OV-25 and 3% Poly-A 103 columns) and confirmed by thin-layer chromatography (system: ethyl acetate/acetone/concd ammonium hydroxide, 100/10/4.5 by vol; reagent: iodoplatinate). As little as 0.5 mg each of codeine and morphine per liter, in free and conjugated forms, is detectable by this method.


Rapid estimation of hemoglobin A2 without chromatography or electrophoresis.

Hemoglobin A2 is batch fractionated with diethylaminoethyl Bio-Gel A (Bio-Rad Laboratories) equilibrated with a tris(hydroxymethyl)aminomethane HCl buffer (pH 7.68, 8.75 mmol/liter, 6.36 mmol of CL- per liter). Hemoglobin A1 and F become bound to the resin, allowing the separation and quantitation of A1. Hemoglobin S alters the equilibrium condition, but adjustments are easily made so that A2 can be separated in the presence of S. The procedure is simpler than electrophoretic or chromatographic methods, requires 5 min, is accurate (A2 fraction is at least 94% A2, less than 6% A1), precise (SD +/-0.24 for duplicates), and has a normal limit of 2.6 +/-1.02%.


Centrifugal analyzer determination of ascorbate in serum or urine with Fe3+/Ferrozine.

Measurement of serum ascorbate may be useful in long-term population studies because of the possible influence of ascorbate on numerous physiological factors. We describe an automated method for determining ascorbate in serum and urine by using the reduction of ferric iron by ascorbate and the formation of a color between the resulting ferrous iron and Ferrozine [3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine]. A centrifugal analyzer is used to rapidly and simultaneously measure ascorbate in the samples and standards and minimize interference from slower reacting substances in the sample. The method is highly precise and specific. Data are also presented on the stability of ascorbate in serum, urine, and aqueous solutions.


Iodination of morphine and dihydromorphine, as related to radioimmunoassay.

Direct iodination of morphine or dihydromorphine with iodine-125 results in products that bind to antibody raised by immunization of animals with a 3-O-carboxymethylmorphine/bovine serum albumin immunogen. Iodination of morphine or dihydromorphine with iodine-127 under identical conditions failed to yield these immunologically active products, suggesting that the results obtained with iodine-125 are in part due to a radiolytic reaction not observed with the iodine-127.


Clinical determination of methemalbumin.

We developed an assay for methemalbumin in biological fluids by using diethylaminoethyl-Sephadex ion-exchange chromatography to separate this protein from interfering components, including hemopexin, transferrin, hemoglobin, and haptoglobin/hemoglobin complex. Initial screening of the samples requires measurement of A280/A405 ratios of the peak tubes of the isolated albumin fraction. Values exceeding 30 indicate that methemalbumin is absent, and no further work is required. Values of less than 30 suggest that methemalbumin is present in the original sample, whereupon the presence and amount of methemalbumin can be ascertained by coloremetric assay for iron with use of ferrozine. Results may be expressed either in terms of micrograms of methemalbumin iron per gram of albumin or in milligrams of methemalbumin per liter. The reproducibility of the method is of the order of +/- 7% (SD). Normal persons have essentially no methemalbumin iron in their serum. Three individuals with hemorrhagic pancreatitis showed values of 65, 98, and 198 mug of methemalbumin Fe per gram of albumin.


Evaluation of the ABA-100 procedure for total and direct bilirubin in serum or plasma.

We present a modified Evelyn-Malloy method, adapted to the Abbott Biochromatic Analyzer (ABA-100) for the determination of both total and direct bilirubin. It requires less than 25 mul of serum or plasma. At least 50 samples can be assayed per hour with economy of reagent consumption and the precision compares favorably with that for conventional manual methods.


Evaluation of an automated glucose-oxidase procedure.

We evaluated a slight modification of the automated oxidase/peroxidase method for glucose determination in blood with use of 4-aminophenazone [J. Clin. Pathol. 22, 246 (1969)]. Nonsugar reducing substances did not interfere, except for ascorbic acid in very high concentrations. Lipemic sera gave slightly lower values. Values for reproducibility, specificity, and sensitivity were closer to such values for the hexokinase method than was the case for some other commonly used methods.


Double-antibody radioimmunoassay of serum insulin: effect of use of hormone-depleted human serum.

Human serum can be depleted of insulin and growth hormone by treatment with dextran-coated charcoal or by dialysis, or both. Inclusion of such hormone-depleted serum in the standard curve of a double-antibody radioimmunoassay for immunoreactive insulin more nearly mimics the conditions under which an unknown human serum sample is assayed. Compared to the usual standard curve in which serum albumin is the only protein, the addition of hormone-depleted serum can cause an increase (by an average 64% under the conditions we used) in the absolute value for apparent insulin in serum. The effect of hormone-depleted serum should be tested in the standard curves of double-antibody radioimmunoassays and included routinely in these standard curves if it changes the results. When used in conjunction with an eventual reference standard for human insulin, this modification of the insulin assay may make the measured values of human serum insulin from different laboratories more comparable.


Indirect assessment of hydroxymethylglutaryl-CoA reductase (NADPH) activity in liver tissue.

We describe an indirect method for assessing variation in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (NADPH) activity in liver tissue. 3-Hydroxy-3-methyglutaryl-CoA and mevalonate concentrations in the tissue homogenate are estimated in terms of absorbances and the ratio between the two is taken as an index of activity of the enzyme, which catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoZ to mevalonate. The ratio increases under conditions in which activity of this enzyme in liver reportedly decreases (e.g., fasting, cholesterol feeding) and decreases under conditions in which the activity of this enzyme reportedly increases (e.g., Triton injection, phenobarbital treatment). We assessed the magnitude of hepatic cholesterogenesis in intact male albino rats by using [1,2-14C] acetate, in fed controls, fasted, cholesterol-fed, Triton-treated, and phenobarbital-treated. The ratio, 3-hydroxy-3-methylglutaryl-CoA/mevalonate was estimated in liver tissue for all the above groups. The method is simple, reproducible, and does not require any unusual chemicals.


Defective thyroglobulin export as a cause of congenital goitre.

The thyroids of two brothers aged 13 and 15 with congenital goitre, butanolinsoluble iodine in blood and which had pronounced decrease of immunoreactive thyroglobulin content in the thyroid were studied. Two types of thyroglobulin were identified. The first amounted to only about 200-300 mug/g wet tissue and was fully immunoreactive with anti normal human thyroglobulin antiserum (iTG-G). It was purified by affinity chromatography. The other was mainly associated with intracytoplasmic membranes, amounted to about 8 mg/g wet tissue and was only partially immunoreactive (piTG-G). Both had abnormal amino acid compositions but only iTG-G showed a decreased carbohydrate content. Surprisingly, piTG-G showed a normal iodination level (0-5%) and a normal iodoamino acid composition. Immunochemical studies performed on slices or cell-free fractions incubated in the presence of labelled amino acids and/or monosaccharides showed that: (1) thyroglobulin peptide chains were being synthesized and almost normally discharged into the cisternae of the rough endoplasmic reticulum; (2) incorporation of sugars into iTG-G was decreased; (3) sialyl- and galactosyltransferase activities were normal and the enzymes normally located, and (4) albumin which is present in the thyroid as the iodinated protein was probably not synthesized by the goitrous tissues. Two major abnormalities were detected by light and electron microscopy: absence or pronounced scarcity of colloid in the follicular lumina and overdistended endoplasmic reticulum cisternae. These observations are compatible with a defect in TG transport from the cell into the lumen as the cause of the goitre. Whether defective thyroglobulin export is basically related to abnormality of the protein structure or to another cause is discussed.


Hormonal studies in Klinefelter's syndrome.

Some aspects of the hormonal abnormalities of Klinefelter's syndrome have been studied in nineteen patients. As a group the plasma production rate, the total and free levels of testosterone, and the metabolic clearance rates of testosterone and oestradiol were low. Plasma oestradiol, LH and FSH levels were elevated and there was increased peripheral conversion of testosterone to oestradiol. The production rates of oestradiol and the binding capacities of the sex steroid binding globulin were normal. There were fluctuations in the blood levels of LH, FSH, testosterone and oestradiol, but these appeared to be less marked than in healthy men. Both LH and FSH levels were suppressed by acute or prolonged testosterone administration and there was no evidence for a differential effect on LH. It is suggested that the threshold for suppression of LH and FSH is increased in hypergonadotrophic states. Although no statistically significant relationships were found between the hormonal and clinical abnormalities of the syndrome it is probable that the hyperoestrogenism and androgen deficiency are linked to the development of the signs of feminization and hypogonadism.


Impaired phagocytic activity of human monocytes in respect to reduced antibacterial resistance in uremia.

Resistance to bacterial infection, particularly septicemia and pneumonia, is decreased in patients with uremia. Tests of monocyte function in 21 patients with chronic uremia and in 21 normal healthy subjects showed an increase in attachment rate, spreading activity and Nirtoblue-tetrazolium reduction in the uremic subjects. In contrast, phagocytosis of IgG-coated red cells was impaired.


Short dialysis with a polyacrylonitrilmembrane (RP 6) without the use of a closed recirculating dialyzate delivery system.

Because of excessive eltrafiltration (UF), the RP 6 dialyzer requires a closed recirculating dialyzate delivery system. The purpose of this study is to present the characteristics of the RP 6 dialyzer on a single needle system which programs the UF rate of this dialyzer. The single needle system consists of one blood pu-mp and two roller pump heads, switched on and off at preselected maximum and minimum out let pressures (OP). It is possible to decrease the UF rate by lowering the OP in the bubble trap chamber. By varying OP from 0 to 100 mm Hg, we obtained an UF rate in vitro of 6.5 ml per minute. The clearance values, in ml/min, obtained at OP 0 to -100 NN Hg, QB 300 and QD 500 are (in ml/min): urea: 160.0, creatinine: 145.0, sucrose-C14: 105.4, sodiumiothalamate-i125: 79.9, cyanocobalamin-co58: 73.7 and inulin-3H: 40.7. The priming volume (corn-oil) at OP 0 to -100 MM Hg, QB 250, QD 500 varies between 140 ml (at the minimum OP) and 150 ml (at the maximum OP). We performed 370 dialyses. The dialysis runs were well tolerated: moderate hypotension occurred in 4% and cramps in 1.6% of the dialyses. In most cases no fluid perfusion was necessary. The residual blood volume (Technetium99m) is estimated at 8.2 ml(n equale 11).


The kinetics of aminosidine in renal patients with different degrees of renal failure.

The plasma concentration and urinary excretion after a single 500 mg dose of Aminosidine have been studied in 12 patients with different degrees of renal failure and 4 normal subjects. In normal subjects the plasma half-life is 2.47 hr; in patients with creatinine clearance (Ccr) of 30-60 ml/min, its 6.7 hrs.; in patients with Ccr of 10-30 ml/min, it is 16.7hrs.; in patients with Ccr less than 10 ml/min, it is 36.6 hrs. A dose of 0.5 g of Aminosidine should be given to normal subjects every 12 hr. When renal function is reduced, the interval (in hr) between doses should be the following: Ccr 60-40 ml/min: 19-28;Ccr 40-30 ml/min; 28-35; Ccr 30-20 ml/min: 35-47; Ccr 20-10 ml/min: 47; Ccr less than 10 ml/min: 76.


Cystic disease of the renal medulla associated with retinitis pigmentosa and imino acid abnormalities.

A 22 year old man with renal failure associated with salt wasting, retinitis pigmentosa, and imino acid abnormalities is reported. Renal tissue showed changes compatible with medullary cystic disease or juvenile nephronophtisis. Special studies were carried out to clarify the mechanism of renal salt wasting. Retinal pigmentary changes were found in three siblings and a male cousin; in two siblings studied abnormal retinal function was demonstrated. the parents who were first cousins once removed were normal. Fifty kindred members were examined and none showed unequivocal signs of renal disease. Autosomal recessive transmission of ocular and renal disease appeared likely. The separation of medullary cystic disease from juvenile nephronophthisis on the basis of onset and mode of inheritance is probably artificial.


Prolonged hypercalcemia following acute renal failure.

A case is reported of a twenty-one year old man who developed severe hypercalcemia late in the diuretic phase of acute reversible renal failure secondary to severe trauma. Hypercalcemia persisted for approximately five months. Serum immunoreactive parathyroid hormone levels were undetectable and sub-total parathyroidectomy had no appreciable effect on the serum calcium. The most likely source of this patient's hypercalcemia was resorption of calcium from metastatic deposits in soft tissue and possibly from bone. Failure to incorporate calcium into bone during the period of immobilization may explain the prolonged hypercalcemia.


Complications of percutaneous femoral vein catheterizations for hemodialysis.

Five life threatening complications of percutaneous femoral vein catheterization for hemodialysis (Shaldon Technique) are presented. They occurred over a period of five years during which 700 uneventful catheterizations were carried out. In three instances femoroiliac vein thrombosis occurred, and on one occasion this was complicated by pulmonary embolism. In two other instances perforation of the inferior vena cava occurred with profuse bleeding. These complications can be aboided by early removal of the catheters after dialysis and by cautiously manipulating the wireguide when resistance or obstruction is encountered during insertion.


Bartter's syndrome: clinical study of its treatment with salt loading and propranolol.

The clinical course of a 9 year old black male with Bartter's syndrome who has been followed since age 1 1/2 years is presented. He had been unable to conserve sodium on a low salt diet and has failed to show improvement in serum electrolytes while on a sodium loading regimen. He is now refractory to spironolactone and KCI therapy, even in conjunction with supplemental sodium. On two separate trials his electrolytes have approached normal with the combination of propranolol and spironolactone along with KCI and NaCl supplementation. However, his response to this regimen has been a temporary one with relapse to the pretreatment chemical status despite increasing doses of propranolol and potassium chloride.


Platelet function in dialyzed and non-dialyzed patients with chronic renal failure.

Platelet function studies were performed on healthy volunteers, patients with stable chronic renal failure, hospital dialysis patients and home dialysis patients. In the non-dialyzed patients with chronic renal failure, there was inverse exponential relationship between serum creatinine and platelet adhesiveness indicating progressive impairment of platelet adhesiveness with creatinines in excess of 6 mg/100 ml. In the dialysis population there was an inverse linear relationship between platelet adhesiveness and pre-dialysis creatinine values. Platelet aggregation by ADP was normal in chronic renal failure patients with serum creatinines less than 6 mg/100 ml but was impaired in others. Both groups of dialysis patients also had impaired platelet aggregation but improvement appears obtainable by home dialysis. The results suggest that in chronic renal failure, platelet function is normal until serum creatinine exceeds 6 mg/100 ml and thereafter progressively deteriorates. Improvement is not obtained by 12 m2 hours of hospital dialysis but is by 18 m2 hours per week of home dialysis. Platelet function studies may be of value in assessing the adequacy of dialysis.


Creatinine excretion and total body potassium in renal failure.

Total body potassium (TB K) and daily urinary creatinine excretion were measured in 12 patients with mild chronic renal disease (CCr/1.73 m2 BSA greater than 40 ml/min, Group I) and 12 patients with severe renal disease (CCr/1.73 m2 BSA less than 19 ml/min, Group II). Creatinine excretion as a function of total body potassium was significantly lower in the males and females of Group II as compared to males and females in Group I. TB K was linearly related to creatinine excretion in both groups of patients. Mean TB K was not significantly different from mean predicted normal values (TB Kp) in both groups. The decreased creatinine excretion observed in severe renal failure cannot be due to a significant loss of lean body mass because TB K was not significantly decreased below predicted normal values. Decreased creatinine biosynthesis, alternate routes of excretion, metabolic reutilization, or conversion of creatinine to other metabolites may have contributed to the decreased creatinine excretion noted in this group of patients with renal failure.


Recurrent hemolytic-uremic syndrome: a case report.

A girl who developed HUS at 2 years of age had four further episodes of the disease during the next 2 1/2 years. No renal or hematologic abnormalities were detected during or between the attacks. Reduced levels of serum complement were found during three of the episodes.


Ultrastructure of the sternocleidomastoid muscle in muscular torticollis.

The sternocleidomastoid muscles from five children with muscular torticollis--examined by transmission electron microscopy, exhibited a marked increase in interstitial collagen deposition, and scattered areas of amorphous ground substance with electron dense deposits. No vascular abnormalities were observed. Ultrastructural muscle abnormalities showed various stages of immobilization degeneration including nearly complete loss of myofibrils. The muscle abnormalities ultrastructurally are consistent with immobilization degeneration, probably secondary to the marked fibrosis in the sternocleidomastoid muscle.


Luxatio erecta of the hip. An interesting case report.

This is a case report of an inferior dislocation of the hip in a 5 1/2-year-old child, characterized by acute flexion with slight abduction of the hip and flexion of the knee. The dislocation is reducible by traction in a cephalad direction, gradual extension and internal rotation of the hip.


Neonatal diagnosis, treatment and related factors of congenital dislocation of the hip.

The unstable hip can be diagnosed in newborns with acceptable accuracy. The following factors are associated with the newborn unstable hip: female preponderance, breech presentations, cesarean section deliveries, first borns, left hip involvement, the Caucasian race, and increased birth weight. These findings suggest that the newborn unstable hip is determined prior to delivery, possibly within the last 4 weeks of intrauterine life. Diagnosed at birth, treatment in the average case is relatively short-term, effective, and without complication.


Tuberculosis of the hip. Treatment with closed irrigation and suction using streptomycin.

In 51 children with tuberculosis of the hip, overall end results were better, and the range of motion was improved when irrigation-suction with Streptomycin was included in the regimen of surgical management.


External rotation contracture of the extended hip. A common phenomenon of infancy obscuring femoral neck anteversion and the most frequent cause of out-toeing gait in children.

External rotation contracture of the extended hip is common in young infants, decreasing progressively with growth so that it appears to be present in less than 5 per cent of the children over age 18 months. Persistence of the external rotation contracture was the main cause of toeing-out gait in this study. Femoral neck anteversion, as a cause of internal rotation posturing of the limb, does not become clinically recognizable until complete resolution of the external rotation contracture of the hip has occurred, that is, usually after 18 months of age. Femoral neck retroversion was not present clinically in any of the patients examined, and so appears to be quite rare. Approximately 80 per cent of children under 18 months of age who toe-in have internal tibiofibular torsion; most of these also have significant talar neck adductus! Approximately 70 per cent of children over age 2 years who toe-in have excess femoral neck anteversion as the cause. Approximately 75 per cent of the children with metatarsus adductus deformity have coexistent internal tibial torsion and talar neck adductus; only 25 per cent of children with internal tibial torsion have coexistent metatarsus adductus deformity. Physiologic genu varum usually occurs prior to 2 years of age and physiologic genus valgum usually occurs after 2 years of age.


Epiphysiolysis of the proximal femur in very young children.

In 14 hips in 11 children under 3 years of age, proximal femoral epiphysiolysis occurred from varying degrees of trauma. The vulnerability of the blood supply of the upper femoral epiphysis, and its important weight-bearing function, demands early diagnosis, reduction, and adequate fixation. The nature of the injury, however, determines the eventual outcome. Early diagnosis and investigation of the underlying pathology is necessary to avoid such complications as varus deformity, avascular necrosis, heterotopic new bone formation, non-union, and premature closure of the growth plate.


Subtrochanteric fractures of the femur in children.

Subtrochanteric fractures are relatively rare in children and usually result from severe trauma. The unique biomechnical forces about the hip following fracture tend to complicate treatment. Remodeling and growth stimulation generally ensure good results by nonoperative means in children under 10 years of age. Open reduction should be considered in older children when good alignment cannot be achieved by closed methods.


Anterior slip of the capital femoral epiphysis. Report of a case and discussion.

A rare case of anterior slip of the capital femoral epiphysis demonstrates that the mechanism of the posterior, inferior slip of the capital femoral epiphysis is a combination of weight bearing in the frontal plane and muscle pull in the horizontal plane. Sudden violent motions cause some of the unusual positions of acute slip.


The patella index as a guide to the understanding and diagnosis of patellofemoral instability.

An analysis of 1004 X-rays has demonstrated that the medial patella facet is significantly smaller in patients with patellofemoral instability. There is no such significant difference in the width of the whole patella. Therefore the longitudinal ridge separating the smaller medial facet from the larger lateral facet must be closer to the medial patella border. As this ridge articulates with the groove between the femoral condyles, its medial position is accounted for by the patella being more laterally positioned in patients with patellofemoral instability.


Non-union of the clavicle in a child. A case report.

A case of symptomatic non-union of the clavicle occurred in a 12-year-old boy. Differential diagnosis roentgenographic and histologic observations, including the results of resection of the non-union site and stablization of the proximal clavicle using the coraco-acromial ligament demonstrated that this rare condition can be restored to full asymptomatic function without any internal metallic fixation devices.


Slipped capital femoral epiphysis following ipsilateral femoral fracture.

Two cases of femoral fracture with a subsequent complication of ipsilateral slipped capital femoral epiphysis point out the possible deleterious effects of angular deformity of the proximal femur during the adolescent growth spurt.


Congenital pseudarthrosis of the tibia: successful one stage transposition of the fibula into the distal tibia. A case report.

An infant male presented at age 17 months with an established pseudarthrosis in a kyphoscoliotic right tibia. During the ensuing 6 years, three unsuccessful McFarland bypass bone grafts were performed. Then the distal end of the proximal fibula was placed into the medullary cavity of the proximal end of the distal tibia without disturbing the proximal portion of the fibula. This was augmented by autogenous bone graft. Union occurred in one year. The child has been followed for 7 years and the pseudarthrosis remains healed.


Comminuted epiphyseal fracture of the distal tibia. A case report and review of the literature.

Classification of epiphyseal injuries include only simple fractures and few cases of comminuted fracture of the distal tibial epiphysis, epiphyseal plate and adjacent metaphysis. On the basis of a review of the literature, as well as our own experience, it appears that that fracture is unstable and requires open reduction and internal fixation.


Pitfalls in the diagnosis of Osgood-Schlatter disease.

One patient with osteomyelitis of the anterior tibial tubercle and a second patient with arteriovenous malformation of the anterior tibial tubercle were originally misdiagnosed as having Osgood-Schlatter disease. These patients demonstrate pitfalls in the diagnosis of Osgood-Schlatter disease.


Congenital metatarsus varus. A suggestion for a possible mechanism and relation to other foot deformities.

The pathogenesis of metatarsus varus was investigated by a series of dissections of 14 normal feet of stillborn or infants who died during the perinatal period. The deformity could not be produced without the surgical incisions described below. A valgus position of the hindfoot was produced by maximal dorsiflexion of the foot. The deformity of the fore part of the foot could not be produced even by extreme traction on the tibialis anterior tendon even after capsulotomy of the first tarsometatarsal joint. Only extensive capsulotomies in the tarsometatarsal joints distal to the joint of Chopart made it possible to displace the bones into the position analogous to metatarsus varus. It is suggested that metatarsus varus may be a deformity which occurs on a maximally dorsiflexed foot and that the primary mechanism of the forefoot deformity is a subluxation in the fore part of the foot. Secondary contractures of the soft tissues, and adaptive bone changes offer a possible explanation for lack of spontaneous recovery as well as the difficulties encountered in treating late cases.


Section of the abductor hallucis tendon for correction of metatarsus varus deformity.

Section of the abductor hallucis tendon is recommended for early correction of the metatarsus adductus deformity especially in the residual of a treated equinovarus foot. The operation is simple and safe, with very little postoperative morbidity. The effectiveness of the procedure is enhanced if a tight abductor hallucis tendon is demonstrated. The operation may also be helpful in conjunction with other surgical procedures for correction of the varus deformity of a clubfoot.


Trisomy 8 syndrome.

Trisomy 8 syndrome, with or without mosaicism, is characterized by the following clinical signs and symptoms: mental retardation, deformed skull, prominent forehad, high-arched palate, low-set and/or dysplastic ears, long and slender trunk, reduced joint mobility, and deep plantar furrows. The deep furrow or longitudinal crease of the sole may be pathognomonic for the syndrome. It should be noted that it has been seen in other rare syndromes. It is recommended that a child with mental retardation and associated multiple anomalies should be subjected to a cytogenetic study in order to define the incidence of this syndrome. Differnetial diagnosis should include: Fong's syndrome, arthrogryposis and otopalato-digital syndrome. It is interesting to note that there seem to be individuals who have had no physical abnormalities and have been identified during an evaluation for repeated abortions. The above described case of trisomy 8 mosaicism was seen and treated for many years by many different specialists without an accurate diagnosis.


Osteoid-osteoma inducing pronounced overgrowth and deformity of bone.

A rare complication of osteoid-osteoma is localized overgrowth and/or deformity of bone. Six of 64 cases reviewed had this growth disturbance. All patients developing deformities had their onset of symptoms before 5 years of age. Not one of the patients had limb equalization or correction of the deformity after removal of the osteoid-osteoma. The longest follow-up was 8 years. Speculations on the underlying cause for this form of growth abnormality, and the incidence in infants and very young children suggests that immediate surgical treatment is the best course of action.


Orthopedic management of acquired cerebrospasticity in childhood.

Of 221 children with head injuries and resultant deep coma followed for long-term problems, 156 became totally independent, functional individuals, only 61 lacking normal cognition and speech. Reconstructive surgical procedures for residual spasticity was necessary in 45 patients. Achilles lengthenings were the most common procedure performed; after Achilles lengthenings, toe flexor releases were most often required. Twenty children had anoxia from drowning or anesthesia problems; 7 of these had spastic hip deformities or dislocations, all within 6 months of the anoxic event. Progressive cerebrospastic syndromes and post-infectious cerebrospasticity most often require orthotic devices for their orthopedic management.


Normal ranges of hip motion in infants six weeks, three months and six months of age.

Flexion contracture, internal rotation and external rotation of the hip were reported in 40 infants at 6 weeks and 3 months and in an independent sample of 40 infants at 6 months of age. Population means and normal ranges of motion were determined for use in the evaluation of hip problems and their treatment. A mean hip flexion contracture of 19 degrees was present at 6 weeks of age, decreasing to 7 degrees by three months, but still persisting at 6 months suggesting that forceful extension of the hip in infants may be contraindicated. Hip flexion contracture decreased in every child from 6 weeks to three months. In all cases, external rotation was greater than internal rotation. Internal rotation greater than external rotation before the age of 6 months appears contrary to normal development. There was a significant correlation between the changes in hip flexion contracture and internal rotation from 6 weeks to 3 months. An interesting extension of this study would be a longitudinal follow-up of infants beyond 6 months of age to further define these developmental trends.


On the origin of cells in heterotopic bone formation.

Previous experiments have demonstrated that decalcified, lyophilized bone matrix is a powerful substratum for differentiation of mesenchymal cells into new bone. The present experiment employs parabiosis as a tool to distinguish between cells of hemotogenous origin and mesenchymal cell populations derived from the site of implantation of bone matrix. The results indicate that the osteoinductor releasing cells are blood-borne monocytoid cells which enter the tissues by diapedesis and become histiocytes, macrophages, matrixclasts and osteoclasts; their precursors are derived from bone marrow at sites remote from the area of bone induction. The cell populations responding to the osteoinductor released by this mechanism develop into osteoblasts and osteocytes and are the progeny of perivascular mesenchymal cells.