Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat. Hyperresponsiveness of resistance vessels has been described in various vascular beds of spontaneously hypertensive rats perfused with artificial medium. This change has been attributed to altered vascular dimensions secondary to the development of hypertension. To test the possibility that true changes in sensitivity might contribute independently to vasoconstrictor hyperresponsiveness in spontaneously hypertensive rats, threshold vasoconstrictor doses of norepinephrine and barium chloride were determined in denervated hindquarters of rats perfused at constant flow with autologous blood. Threshold constrictor responses to norepinephrine were elicited in the hypertensive rats at concentrations averaging less than one-third that required in controls. Threshold vasoconstrictor concentrations of barium were not significantly different between the two groups. The ratio of norepinephrine/barium sensitivity was also significantly elevated in the hypertensive group. These data suggest that in the presence of a full humoral complement, excitability (barium sensitivity) in resistance vessels of spontaneously hypertensive rats is not altered, whereas the smooth muscle is hypersensitive to norepinephrine. Thus, it appears that changes in sensitivity as well as altered vascular geometry are important in the production of vascular hyperresponsiveness in the spontaneously hypertensive rat.


Angiotensin III:  (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Evidence is reviewed that three and possibly four peptides formed from renin substrate have biological activity that merits their recognition as agonists. The decepeptide angiotensin I affects sites in the central nervous system and adrenal medulla. The octapeptide angiotensin II affects vascular and cardiac sites that mediate acute pressor responses, and also causes direct feedback inhibition of renin release. The heptapeptide (des-asp-1)-angiotensin II ("angiotensin III") stimulates aldosterone release.. It may exert its effects intracellularly at the adrenal glomerulosa and other sites. The fourth candidate is the (des-asp-1)-angiotensin I nonapeptide, but nothing is known of its activity or circulating levels. This formulation of the angiotensin reaction sequence and the effects of its individual congeners suggests several experiments. It also permits simple explanations for previously confusing data, such as the inability of immunization and anti-angiotensin II to prevent aldosterone responses, and the paradoxical preservation of adrenal responsiveness in Bartter's syndrome.


Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs. The aldosterone response to long-term infusion of angiotensin II and potassium was studied in intact conscious dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), and plasma cortisol concentration (PCC) were determined by radioimmunoassay. In ten dogs maintained on angiotension II infusion (5 ng/kg min-1) for 14 days, PAC increased from 6.9 plus or minus 2.9 to 18.6 plus or minus 4.7 ng/100 ml plasma (mean plus or minus SE) within ten minutes after beginning the infusion, reached a maximum level of 28.3 plus or minus 6.8 ng/100 ml plasma by one hour, and returned to control levels by six hours. PCC increased from 0.6 plus or minus 0.2 to 3.9 plus or minus 1.0 mu-g/ 100 ml plasma within one hour after angiotensin II infusion and returned to control levels by six hours. During the next 14 days of angiotensin infusion, PAC remained at control levels, PRA was undetectable by radioimmunoassay, and mean arterial blood pressure was elevated 29 plus or minus 4 mm Hg above control levels. In ten dogs maintained on KCL infusion (250 mEg/day) for 15 days, PAC increased from 6.8 plus or minus 2.4 to 13.6 plus or minus 3.4 ng/100 ml plasma within 24 hours, averaged 22.4 plus or minus 4.3 ng/100 ml plasma by 48 hours, and remained elevated for the next 12 days, averaging 21.8 plus or minus 5.6 ng/100 ml plasma. During the next 14 days of KCL infusion, serum Kn increased from 4.1 plus or minus 0.3 to 4.9 plus or minus 0.5 ME1/L, and PRA decreased from 1.25 plus or minus 0.3 to 0.65 plus or minus 0.2 ng/ml/hr. PCC averaged 0.73 plus or minus 0.4 mu-g/100 ml plasma in the control samples and failed to change significantly during KCL infusion. These data indicate that chronic angiotensin II infusion into intact conscious dogs at rates capable of maintaining elevated arterial blood pressure results in a transient increase in aldosterone secretion that lasts only a few hours, while chronic infusion of potassium ions at rates that produce a minor increase in serum Kn results in a sustained increase in aldosterone secretion.


Prostaglandin synthesis by bovine mesenteric arteries and veins. Prostaglandins (PG) were synthesized at similar rates by bovine mesenteric arteries and veins; viz., ca. 200 ng/g wet weight after one hour of incubation. After synthesis, PGE and PGF compounds were released from slices of arteries and veins into the incubating medium; PG were not detected in the walls of these blood vessels. Arachidonic acid, the precursor to PGE-2 and PGF-2-alpha, did not affect PG synthesis, whereas meclofenamate, an aspirin-like agent, decreased synthesis in arteries and veins by 90%. The PG biosynthetic capacity of these blood vessels is high, as indicated by greater than 20% conversion of (1-14C)-arachidonic acid to radiolabeled PG. Under control conditions in both arteries and veins, synthesis of PGE-2 exceeded that of PGF-2-alpha twofold. Bradykinin selectively increased the synthesis of a PGE-like substance in arteries and of a PGE-like substance in veins.


Renal prostaglandin synthesis in the Goldblatt hypertensive rat. The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.


A clinical and follow-up study of right and left bundle branch block. The experience with bundle branch block at the USAF School of Aerospace Medicine was reviewed. The clinical and follow-up status was evaluated in 394 subjects with right bundle branch block (RBBB) and 125 subjects with left bundle branch block (LBBB). The majority of subjects were asymptomatic at the time of bundle branch block diagnosis. The subjects were divided into subfroups based on electrocardiographic (EEG) findings to determine if any one subfroup was at higher risk for initial or follow-up morbidity of cardiobascular disease or follow-up mortality. At initial diagnosis and clinical evaluation, 94% of RBBB and 89% of LBBB subjects had no evidence of cardiobascular disease. In the RBBB group, 3 and 2%  had cornary heart disease and hypertension, respectively; in LBBB subjects, 9 and 7% had cornary heart disease and hypertension, respectively. No one ECG subfroup in either the RBBB or LBBB group had a higher incidence of cardiobascular disease. Complete follow-up information was available in 94% of the RBBB subgroup subjects and 91% of the LBBB group. In the follow-up period, new cases of coronary heart disease and hypertension occurred in 6% of the RBBB group and 5 and 8%, respectively, in the LBBB group. Fourteen (4%) RBBB and nine (8%) LBBB subjects died during the follow-up period. No differences for follow-up groups. Progressive electrical dysfunction in the form of complete heart block occurred in one subject each absence, and degree of associated cardiobascular disease. Furthermore, within the age limits of the present aeromedical implications of bundle block are discussed.


Echocardiographic observations on ventricular septal rupture complicating acute myocardial infarction. Echocardiograms were performed on three patients with ventricular septal rupture complicating myocardial infarction. The pulmonary artery mean pressure was 30 mm Hg or more in all three patients. The size of the ventricular septal defect, determined at operation or autopsy, was 2 cm or greater in each patient. The salient echocardiographic abnormality was dilatation of the right ventricle. The direction of septal motion was normal in all the patients. The left atrial diameter was slightly increased in one patient and was normal in the other two. In one patient, and unusual pattern of mitral valve motion was seen. Complete closure of the reopening of the valve. This pattern was suggestive of increased blood flow through the mitral valve. Although some of these findings are nosspecific, the combination of echocardiographic findings may provide useful clues to the diagnosis of septal perforation.


True and false left ventricular aneurysms. Propensity for the altter to rupture. Two cases are described of sudden death resulting from rupture of small chronic false aneurysm of the left ventricle with secondary hemopericardium. The cases support the point that rupture of chronic false left ventricular aneurysm tends to occur. This appears to be contrary to the potential for chronic true aneurysms of the left ventricle which tend not to rupture. Rupture of true left ventriuclar aneurysm in its deveoping stahe may, however,  occur.


Electroide cather recording during malignant ventricular arrythmia following experimental acute myocardial ischemia. Evidence for re-entry due to conduction delay and block in ischemic myocardium. In 20 anesthetized opened-chest dogs, plunge wire and electrode catheter recordings of the this bundle electrogram which also showed septal activation, were monitored before and after ligation of the anterior septal artery. The average time to onset of ventricular tachycardia after ligation was 5-1/2 min. The evolution of the arrhythmia was temporally related to progressive fragmentation and delay of the septal potential, resulting in a marked increase in total ventricular activation time (up to 335 msec). In six experiments the fragmented, delayed septal depolarization was inscribed well beyond the T wave of the surface QRS prior to the onset of arrhythmias. Various conduction disorders involving the ischemic septal myocardium were observed which closely correlated to the patterns of conduction disorder in the ischemic proximal His-Purkinje system. First degree block, 2 degree block of the Mobitz II and Wenckebach types, higher degree block and paroxysmal complete block occurred. The onset of the arrhythmia was characteristically associated with a Wenckebach pattern of conduction delay of a part of the septal deflection. Conduction disorders of the ischemic myocardium were tachycardia-dependent. Bradycardia resulted in recovery of form, duration, and timing of the septal potential with the coincident disappearance of ventricular arrhythmias. The study shows that the basic prerequisites for re-entry do exist during the early period following occlusion of a major coronary artery and can explain the malignant phase of ventricular arrhythmias. Similar disorders in man may be detected by intracardiac electrode catheter recordings.


Transient ST-segment in unstable angina. Clinical and hemodynamic significance. The significance of the direction of the ST-segment shifts on the 12-lead electrocardiogram was evaluated in 82 consecutive patients with unstable angina. Eighteen patients with ST-segment elevation (group I) were compared with 64 patients with ST-segment depression (group II). There was no difference between group I and group II with regard to age, sex, or history of previous myocardial infarction. There also was no difference in the angiographic extent, location or severity of the coronary artery disease, collaterals, or resting hemodynamics. A larger proportion of patients in group I presented with recent onset angina. Life-threatening arrhythmias were more frequent in group I but were uncommon in both groups. A normal resting electrocardiogram was associated with normal ventricular function in both group I and group II  but was associated with single vessel disease only in group I. An abnormal resting electrocardiogram was associated with multiple coronary vessel disease and abnormal ventricular function in both groups. Single vessel disease was encountered twice as frequently in group I but this difference was not statistically significant. Left main coronary artery disease was found only in group II.


Double accessory pathways in Wolff-Parkinson-White syndrome. Intracardiac electrophysiological studies were performed in two patients with Wolff-Parkinson-White (WPW) syndrome. Atrial pacing at increasing rates or shorter coupling intervals produced inscription of the forward His bundle deflection at progressively longer intervals after the onset of ventricular depolarization. There was an associated increase in QRS duration without any change in the P-R (or St-V) interval. This response was consistent with a Kent bundle. Case 1 also had a short A-H interval which did not show the expected prolongation with stimulation at progressively faster rates. This suggested the presence of a James bundle in addition to the Kent bundle. In case 2 beats conducted exclusively through the atrioventricular (A-V) node had a short H-V interval but a delta wave was not inscribed. Absence of an initial slurring was attributed to the existence of an infra-His bundle bypass of the Mahaim type causing only slight pre-excitation, which was not of sufficient magnitude to be recorded by body surface leads. However, the existence of a congenitally short anterosuperior division of the left bundle could nt be excluded.


Postoperative left anterior hemiblock and right bundle branch block following repair of tetralogy of Fallot. Clinical and etiologic considerations. Previous reports have indicated an incidence of right bundle branch block (RBBB) and left anterior hemiblock (LAH) pattern varying from 8-22% following corrective surgery in patients with tetralogy of Fallot. Among 207 patients with tetralogy of Fallot operated on at our institution, 8.7% developed an ECG pattern of RBBB and LAH. These patients were followed for 1-13 years (mean 6.2 years) for a total of 111 patient years. All patients are alive and none have had documented late atrioventricular dissociation, syncope, or other symptoms. Transient heart block was present in one patient in the immediate postoperative period but has not recurred. This group of patients differs significantly from other series in which such an ECG pattern was associated with a marked increase in morbidity and mortality. These data and the experimental evidence suggest that two distinct groups of patients exist: 1) a group in which this ECG pattern is secondary to lesions within the bundle of His and 2) a group in which the pattern is caused by lesions in the peripheral conduction system. It is postulated that these two groups which demonstrate the same ECG pattern may carry significantly different prognoses. Analysis of H-V intervals postoperatively may help identify patients at risk.


Purkinje repolarization as a possible cause of the U wave in the electrocardiogram. Our recent clinical studies suggest that the U wave represents Purkinje repolarization. To test this hypothesis, transmembrane potentials of Purkinje fibers (P) and the ventricular muscle (V) were simultaneously recorded from canine P-V preparations perfused in a tissue bath, and effects of various factors causing prominent U waves were studied. These include low stimulating frequency (bracycardia), low potassium (K) concentration, hypothermia, and quinidine. Bracycardia increased the difference between action potential duration of P and V, and decreased the rate of repolarization in P. Similarly, the difference of P and V action potential duration was increased markedly by low K and hypothermia, and slightly by quinidine, while the slope of phase 3 was significantly decreased by all these factors. In several intact animals either hypokalemia or hypothermia was produced using hemodialysis or extracorporeal circulation, and recorded electrocardiograms were compared with the P and V action potentials obtained under similar perfusing conditions in subsequent tissue bath study. Such comparison revealed a good temporal correlation between phase 3 repolarization in P and the electrocardiographic U wave. These results, although indirect, appear to support the theory that P repolarization caused the genesis of the U wave.


Follow-up of mass screening for coronary risk factors in 1817 adults. The prevalence of coronary risk factors was assessed in 1,817 asymptomatic adults in Long Beach, California, at the beginning and end of a 10-11 month interval. The risk factors evaluated were hypercholesterolemia, hypertriglyceridemia, hypertension, smoking, hyperglycemia, and marked obesity. The results of the tests were sent to the participants and to their physicians. An educational program aimed at reducing coronary risk factors was offered to the first 1,250 persons screened. Eight hundred and seventy-two of those 1,250 allocated to the education group returned for a second screening. The prevalence of 0, 1, 2, 3, 4, 5, or 6 coronary risk factors did not change significantly between the two screens in either the total group of 1,817 adults or in the 872 adults in the educational program. The Long Beach Heart Association mass screening program for coronary risk factors was ineffective in reducing the number of coronary risk factors.


The effect of cold air inhalation on again pectoris and myocardial oxygen supply. Inhalation of cold air (-20 degrees C) for four minutes provoked angina pectoris in four of 17 coronary disease patients at rest and in four of seven of the patients while they were paced at a heart rate level which was subanginal at room temperature. The cold air did not increase myocardial O2 consumption significantly, and the accompanying changes in systemic hemodynamic factors known to influence myocardial O2 consumption were minor. Coronary blood flow determined by the xenon clearance method did not change significantly. In 18 patients, cold air inhalation for 1 1/2 minutes caused no detectable constriction of coronary arteries visualized arteriographically. We conclude that angina pectoris induced by breathing cold air cannot be explained satisfactorily by a concurrent increase in myocardial work and O2 consumption. Although neither large coronary artery constriction nor generalized coronary arteriole constriction seem to be involved, some other specific effect of cold air inhalation on coronary vasomotion, perhaps affecting collaterals or coronary blood flow distribution, is suspected.


Pathology of stable and unstable angina pectoris. The clinical and pathological data from 46 patients who died during or shortly after coronary bypass surgery and one patient who died shortly after angiography were studied. Each patient was placed into one of three clinical categories of angina pectoris. Twelve were classified as having unstable angina pectoris, 20 as stable severe angina, and 15 as stable moderate angina. No significant difference was found between the three catagories whem age, sex, presence of hypertension, lipid abnormalities, diabetes, smoking, family history of myocardial infarction, or history of previous mycardial infarction were examined. Most patients in all classes of angina had extensive atherosclerotic coronary disease: 12 patients had triple vessel plus left main disease; 25, triple vessel disease; nine double vessel disease; and only one, single vessel disease. There was no difference in severity or distribution of coronary disease when the three catagories of angina were compared. Thirty-six of the 47 patients had evidence of scarring of one or more aspects of the left ventricular wall. There was likewise no significant difference between extent and distribution of myocardial scarring between the three clinical categories. Four of the 12 patients with unstable angina pectoris had pathologic evidence of preoperative myocardial infarction, whereas this was not found in any of the 35 patients with stable angina.


Hemodynamic and prognostic findings in patients with transmural and nontransmural infarction. One hundred and eleven patients with transmural (TMI) and 49 with nontransmural myocardial infarction (NTMI) underwent hemodynamic investigation within 24 hours of onset of symptoms. Patients with NTMI were subdivided into those with ST-segment or T-wave changes alone with a normal QRS complex (NTMI-A) and a group with QRS abnormalities that did not satisfy the criteria for TMI (NTMI-B). Those with TMI had a significantly higher peak creatine phosphokinase (CPK) than those with NTMI: 840 plus or minus 99 and 336 plus or minus 69, respectively, P smaller than 0.05. There was not difference in peak CPK between those with NTMI-A and B. The incidence of arrhythmias and cardiac failure, and routine hemodynamic findings except for left ventricular filling pressure were similar in those with TMI and NTMI. There was not significant difference in in-hospital mortality between those with TMI (22%) and NTMI (33%). There was however a significant difference in in-hospital mortality between those with NTMI-A (0%) and NTMI-B (27%, P smaller than 0.05). The late mortality in those surviving their initial hospitalization was also not different between those with TMI (18%) and NTMI (19%) during a mean follow-up period of 20.2 months. In contrast to the in-hospital mortality those with NTMI-A had a late mortality similar to those with NTMI-B and those with TMI.


Compensatory changes of the distal coronary vascular bed during progressive coronary constriction. The degree and effectiveness of compensatory changes in the distal coronary vascular bed during progressive proximal coronary stenosis have not been described. In this study, coronary vascular bed resistance and pressure gradient-flow relationships were determined for 157 different stenoses in nine opened-chest dogs by measuring coronary flow, aortic pressure, and coronary pressure distal to a coronary constrictor while flow was varied from resting to maximal values by the intracoronary injection of Hypaque-M, 75% (previously shown to cause transient, maximal vasodilatation comparable to ten second occlusion). This approach provided a means of hemodynamically characterizing coronary stenoses in a standary, experimental manner for quantitative analysis of different arteries at different flow rates as found in the intact coronary circulation. The results show that 1) pressure gradient-flow characteristics or hydraulic resistance of stenoses do not become abnormal enough to alter normal resting coronary flow nor to elicit compensatory changes for stenoses up to constriction of approximately 60% of the diameter, 2) compensatory vasodilatation of the distal coronary vascular bed maintains near normal resting flow for lesions between 60% and 85% diameter stenosis but adaptive vasodilatation fails to compensate for the high resistance of lesions greater than 85% diameter stenosis, and 3) there is vasodilator reserve still present when total coronary artery flow is reduced below normal by a stenosis. This vasodilator reserve probably exists in the epicardium since the endocardium is characteristically underperfused due to the low coronary pressure caused by stenosis and is therefore likely to be maximally vasodilated with no remaining vasodilator reserve.


Influence of hypertonic mannitol on ventricular performance and coronary blood flow in patients. The influence of a relatively small increase in serum osmolality produced by hypertonic mannitol on ventricular and systemic arterial hemodynamics and coronary blood flow was studied in 20 patients undergoing cardiac catheterization. Mannitol given to increase serum osmolality 10 mOsm resulted in a small but significant increase in mean systemic arterial pressure, maximum LV dp/dt, left ventricular end-diastolic pressure and cardiac output but no significant change in heart rate or hematocrit. The most prominent change in the patients studied, however, was in coronary blood flow which increased 39% after mannitol. Patients with severe two and three vessel coronary artery disease had increased in coronary blood flow similar to those in patients without coronary artery disease. The data suggest the need to further evaluate the physiological importance of the increase in coronary blood flow produced by mannitol in patients with coronary artery disease and indicate the possibility that mannitol might be of value in treating certain problems in patients with coronary artery disease,


Continuous recording of direct arterial pressure in unrestricted patients. Its role in the diagnosis and management of high blood pressure. We have compared casual indirect measurements of arterial pressure obtained 1) by the general practitioner (GP) and 2) in the outpatient clinic (OPC) with 24 hour continuous recording of direct arterial pressure in two selected group of unrestricted patients. 1) Eight asymptomatic, untreated patients with suspected hypertension. 2) Eight asymptomatic, treated patients whose indirect pressure readings seemed inappropriately high when considered against a general absence of target organ damage. Both groups showed that usually there was good agreement between arterial pressure recorded indirectly by GP and OPC while continuous recording showed wide variability of systolic and diastolic pressures over 24 hours and a significant fall during sleep. The first groups with suspected hypertension showed that the indirect measurements were not significantly different from the 24 hour direct recording. The second group of patients on treatment for hypertension showed a discrepancy, the direct readings being significantly lower than the indirect. This difference (approixmately 30 mm Hg mean arterial pressure) would explain the lack of target organ damage and may have been due to the effect of exercise augmenting the hypotensive action of drugs or due to a well developed defense reflex which biased the indirect readings.


Smoking and fibrinolysis.

Smoking and fibrinolysis. In order to study the fibrinolytic activity of vein walls in smokers and nonsmokers, 71 randomly selected heavy smokers, i.e., smoking more than 15 g tobacco per day, and 41 nonsmokers from the population group "Men born in 1914 residing in Malmo" were invited to undergo a health examination. When examined after 12 hours' abstention from tobacco, the smokers were found to have the same fibrinolytic activity as nonsmokers. Out of the 71 heavy smokers, 31 refrained from smoking during 8-9 weeks (as monitored with questionaire and COHb-determinations). Neither in those who had abstained from smoking nor in the controls did the fibrinolytic activity differ from that initially recorded. In a randomly selected subsample of 19 individuals examined after only one week's abstention from tobacco, the fibrinolytic activity, after venous occlusion of forearms, tended to be lower in the blood as well as in superficial hand veins, but the difference was not significant. The effect of smoking six cigarettes during three hours was measured. This level of smoking was associated with an increased fibrinolytic activity in blood, measured as euglobulin clot lysis time, and in superficial hand veins. This increase is probably due to the combined effects of nicotine and carbon monoxide.


Great vessel, cardiac chamber, and wall growth patterns in normal children. The purpose of this study was to establish normal echocardiographic measurements of valvular motion, cavity dimensions, great vessel diameters, and right, left and septal wall thicknesses of children ranging in size from infants to full growth. The study group was composed of 205 normal, healthy children for whom echocardiograms and subsequent measurements were performed in a standardized manner. The following measurements were performed: left ventricular end-diastolic and end-systolic dimension, right ventricular end-diastolic cavity dimension, right ventricular end-diastolic anterior wall thickness, left ventricular end-diastolic posterior wall thickness, ventricular septal end-diastolic thickness, maximal left atrail dimension, end-diastolic aortic and pulmonary artery diameter, end-diastolic cardiac and septal depth, maximal aortic leaflet separation, and maximal anterior mitral and anterior tricupsid amplitude. Data are grouped into the fifth, fiftieth, and ninety-fifty percentiles according to body surface area. These graphs allow measurements of a single patient to be compared to normal measurements of individuals with similar body surface area.


The basis for differences in ethanol-induced myocardial depression in normal subjects. The acute effects of ethanol (ETOH) on cardiac function in 32 normal subjects has been studied utilizing systolic time intervals. Seven (group I) 13 (group II), and 12 subjects (group III), reported an average daily consumption of less than 1 oz, 1-2 oz, and more than 2 oz of ETOH, respectively. Progressively higher control values from group I to group III in PEP, PEPI, ICT and PET/LVET were observed (PEP-I vs PEPI-III: P smaller than 0.05; PEP/LVET-I vs PEP/LVET-II and PEP/LVET-III: P smaller than 0.05). There was progressively less change in these variables following acute ETOH (P smaller than 0.02-0.05 in group I; P equals NS in group III, group II intermediate). This indicates some degree of chronic myocardial impairment in group II and especially in group III, which tends to be proportionate to the degree of chronic ETOH exposure. These data are not necessarily disparate with previous reports of little or even a salutary hemodynamic effect of ETOH in normal subjects. Thus, the relative stability of LVET post ETOH, coupled with the observed increase in heart rate, is consistent with previous reports of ETOH-induced rate-dependent increments in cardiac output with unchanging stroke volumes, in spite of the presence of acute myocardial depression. The observations reported herein demonstrate the probable incremental influence of ETOH consumption in a chain of events which may culminate in alcoholic cardiomyopathy.


The effects of right atrial and ventricular pacing on the auscultatory findings in patients with mitral valve prolapse. Fifteen patients with midsystolic clicks associated with mitral valve prolapse were studied in order to assess changed in ausculatatory findings produced by pacing-induced variations in cardiac rate, rhythm, and conduction. As the heart rate was increased in stepwise intervals to the maximum possible extent by right atrial pacing (RAP) in 14 patients, the interval between the Q wave and the click (Q-C) decreased in all cases (21 plus or minus msec/10 beats/min; P smaller than 0.001). In two patients, RAP at rates of and above 118 and 159 per minute, respectively, resulted in disappearance of the click. During right ventricular pacing (RVP) without evidence of atrioventricular (A-V) dissociation on the surface ECG in ten patients, the click was inaudible at all pacing rates in three instances. In all seven of the cases in which the click was audible at the lowest rate of RVP with VA conduction, Q-C was greater and C-S2 less than that in sinus rhythm. As the rate of RVP was increased, Q-C was noted to decrease (26 plus or minus 4 msec/10 beats/min) and C-S2 to increase (19 plus or minus 7 msec/10 beats/min) in all patients. In three patients in whom RVP induced atrioventricular dissociation, the click was seen only in beats closely preceded by a P wave. In ten of 11 patients the click occurred earlier in systole with a postextrasystolic or post tachycardia beat as compared to its appearance after a sinus beat when a shorter preceding diastolic filling period was present (P smaller than 0.001). In the eleventh patient a loud systolic murmur was present during a postextrasystolic cycles. It is concluded that pacing-induced rhythm disturbances can result in disappearance of a midsystolic click or can alter its timing and cause it to mimic sonic phenomena seen in other disease states. The possibility of similar changes taking place as a result of spontaneously occurring disturbances of rate, rhythm, and conduction should be recognized in order that the possible diagnosis of mitral valve prolapse not be overlooked.


Unusual examples of supraventricular re-entrant tachycardias. Programmed electrical stimulation of the heart uncovered unusual findings in four patients suffering from supraventricular tachycardias. They included 1) two supraventricular tachycardias of different location and frequency in the same patient, 2) increase in rate of a re-entrant atrioventricular (A-V) nodal tachycardia followed by the development of 2-to-1 A-V block, 3) a "gap" in A-V conduction and A-V nodal re-entrant tachycardia with 2-to-1 A-V block, and 4) the initiation of atrial re-entrant tachycardia by ventricular premature beats. The examples are given to help elucidate the understanding of mechanisms involved in re-entrant tachycardias and to localize the site of the re-entry circuit.


Report of the Inter-Society Commission for Heart Disease Resources. Optimal resource guidelines for radioactive tracer studies of the heart and circulation. The status of radioactive tracer studies in cardiovascular diagnosis is summarized. Planning guidelines are suggested for a hospital nuclear medical service including a central nuclear medical facility and satellite units, and resource criteria are given for professional personnel including training and duties, equipment, space, and support system. The administrative organization of a nuclear medical service and case loads are discussed. Guidelines for equipment maintenance and quality controls are described.


Cardiopulmonary bypass. Microembolization and platelet aggregation. Particulate microemboli and in vitro platelet aggregation were studied in blood of patients during cardiac operations with an electronic particle size analyzer. A small gradient of microemboli developed on passage of blood through a bubble oxygenator but not through a membrane oxygenator. However, with both types of oxygenators, there was a sustained increase in the volume of microemboli in cardiotomy return blood which was much greater than in aterial blood. After cardiopulmonary bypass with both oxygenators, there was a comparable reduction in the volume of circulating platelets which exceeded that of the hemoglobin concentration, indicating platelet loss exceeded that that expected from hemodilution alone. However, the total volume and mean size of platelet aggregates induced in blood of patients after membrane oxygenation was significantly greater than similar measurements after bubble  oxygenation. This study shows that membrane oxygenation reduces particulate microembolization and preserves platelet function in patients undergoing cardiac operations when compared to bubble oxygenation.


Surgical management of large bronchial collateral arteries with pulmonary stenosis or atresia. Single or multiple large bronchial collateral arteries may provide all or some of the pulmonary arterial blood flow in patients with proximal atresia of the pulmonary artery, and even in patients with only pulmonary stenosis. At the time of corrective surgery such arteries must be ligated in order to provide favorable operating conditions, to avoid cardiac overdistention during repair, and to prevent left-to-right intrapulmonary shunting postoperatively. Their ligation and control require precise preoperative definition of their number, origin, and course, and special intraoperative methods for their exposure. Associated hypoplasia of the pulmonary arteries may be severe enough to preclude corrective operation, but these hypoplastic arteries may enlarge in response to increase of blood flow through them resulting from a surgically created shunt. Experience with 14 surgically managed cases of this type forms the basis for the report.


Blood calcium levels in the presence of arteriographic contrast material. One of the complications of coronary angiography is a sudden and persistant fall in blood pressure. This may be due to the presence of calcium chelating agents in the vehicle of the radio-opaque compounds. Depressed ambient calcium levels are associated with decreased myocardial contractility and when low enough cause electromechanical dissociation. Simultaneous measurements of radial artery and coronary sinus ionized calcium levels in nine patients during intracoronary injection of the contrast agent revealed a lowering of the level of ionized calcium in the coronary sinus to a point that can be expected to be associated with a decrease in myocardial contractility. This ionized calcium depression was more marked and prolonged in patients with arteriosclerosis, some reaching levels which, if persistent, could result in electromechanical dissociation.


Left ventricular wall motion response to intravenous propranolol. The effects of intravenous propranolol on left ventricular wall motion and hemodynamics were studied in 16 patients, 12 with significant coronary artery disease and four with chest pain but no coronary disease. Eight patients received 0.10 mg/kg and eight received 0.15 mg/kg of propranolol intravenously. All underwent atrial pacing at a constant rate. Left ventricular angiograms were performed before and 20 minutes after propranolol. At both doses, propranolol caused no significant change in left ventricular systolic or diastolic pressures, either before or immediately following ventriculography. Cardiac index fell significantly (3.4 plus or minus 0.2 [SEM] to 2.6 plus or minus 0.1 L/min/m-2) with the higher dose only. Of the ten patients with coronary artery disease and adequate ventriculograms, one patient had a normal left ventricle, two had regional hypokinesis, only three had areas of hypokinesis and akinesis, two had dyskinetic and akinetic areas, and two had areas of hypokinesis, akinesis and dyskinesis. No changes in regional contractility occurred with propranolol except for a minimal increase in hypokinesis in one patient at each dosage and equivocal development of a new area of slight hypokinesis in one patient and minimal apex of dyskinesis in another at the higher dosage. Of the four patients without coronary artery disease, two were affected by propranolol, one with initial regional akinesis and dyskinesis had slight worsening with propranolol and one with regional hypokinesis developed a definite new area of hypokinesis. Therefore, propranolol, even in large intravenous doses, resulted in no significant change in left ventricular wall motion in patients with coronary artery disease.


Systemic hemodynamic effects of bethanidine in essential hypertension. Although available elsewhere, bethanidine remains under study in the U.S. and its hemodynamic effects are unreported. Therefore, 29 patients with moderately severe essential hypertension received one of four oral dose levels (0.10, 0.25, 0.35, or 0.50 mg/kg) of the postganglionic sympatholytic drug. Blood pressure was reduced only in the 14 patients receiving the highest dose. This was demonstrated within three hours, first by a significant postural hypotension (upright tilt: +14 before vs -19 mm Hg after, P less than 0.001). This orthostatic hypotension effect was associated with a greater fall in cardiac output (13 vs 22%, P less than 0.025) and a diminished reflective increase in total peripheral resistance (19 vs 6%, P less than 0.01); an attenuated Valsalva maneuver overshoot in the supine position was also observed (42 vs 10%, P less than 0.001). Eight of these 14 patients demonstrated supine hypotension associated with either reduced output and/or resistance. Hence, bethanidine is a rather rapidly acting oral sympatholytic agent which reduces blood pressure by producing: (1) decreasec venous return (especially in upright position), suggesting venodilation; (2) arteriolar dilation (supine and upright) reducing peripheral vascular resistance; and (3) attenuated cardiovascular sympathetic reflective adjustments.


Venous flow velocity, venous volume and arterial blood flow. The relationship of arterial blood flow and venous volume to venous flow velocity was studied in normal subjects. The effects of current modes of treatment in venous thrombosis and of a vasodilator drug on venous flow velocity were also investigated. Total calf flow and venous volume were measured by venous occlusion plethysmography while venous flow axial velocity was determined by the transit time of 131-I albumin from calf to inguinal region. Local intravenous epinephrine administration induced venoconstriction and increased venous flow velocity. Intra-arterial isoproterenol and angiotensin increased and decreased arterial flow, respectively, with no change in venous flow velocity of volume, but local heat increased arterial flow and venous flow velocity with no change in venous volume. Local cold, despite venoconstriction, decreased venous flow velocity accompanied by a decreased arterial flow. Intravenous heparin did not affect venous flow velocity. Intravenous but not oral nylidrin increased venous flow velocity. Therefore venous flow velocity can be significantly increased by venocontriction, by large increases in arterial flow (local heat), and by a parenteral vasodilator drug. These experiements indicate that there is a basis for applying heat but not cold in the prevention and treatment of venous thrombosis.


Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a "no-salt" culture. The Yanomamo Indians are an unacculturated tribe inhabiting the tropical equatorial rain forest of northern Brazil and southern Venezuela who do not use salt in their diet. The group therefore presented an unusual opportunity to study the hormonal regulation of sodium metabolism in a culture with life-long extreme restriction of dietary sodium, with parallel observations on blood pressure. Blood pressures increased from the first to second decade but, in constrast to civilized populations, do not systematically increase during subsequent years of life. In twenty-four hour urine collections on adult male Indians, excretion of sodium averaged only 1 plus or minus 1.5 (SD) mEq. Simultaneous plasma renin activities were elevated and comparable to those of civilized subjects placed for brief periods on 10 mEq sodium diets. Similarly, excretion rates of aldosterone equaled those of acculturated subjects on low sodium diets. The findings suggest that the hormonal adjustments to life-long low sodium intakes are similar to those achieved in acute sodium restriction of civilized man. Parenthetically, these elevated levels of aldosterone and renin were probably the norm for man during much of human evolution and suggest that the values observed in civilized controls are depressed by an excessive salt intake in contemporary diets.


Evaluation of precordial electrocardiographic mapping as a means of assessing changes in myocardial ischemic injury. Precordial electrocardiographic mapping has been proposed as a method for evaluating the extent of myocardial injury in patients with acute myocardial infarction. To assess the relationship between direct measures of myocardial cell damage and findings obtained by precordial mapping, the left anterior descending coronary artery (LAD) was occluded in dogs instrumented for simultaneous recording of epicardial and precordial electrocardiograms. The sum in millivolts of ST-segment elevation recorded from 30 electrodes placed in a Silastic grid sutured to the epicardium (EPIsigmaST) was compared to that recorded from 30 precordial electrodes (PresigmaST). While ischemic injury was: 1) maintained constant with a fixed occlusion; 2) reduced by partial reperfusion; 3) increased by addition of a second occlusion; or 4) increased repeatedly by intermittent infusions of isoproterenol, EPIsigmaST and PresigmaST were always closely correlated in each of the 16 dogs studied: r equal 0.92 plus or minus 0.01 (SEM). In seven control dogs, 30 minutes after coronary occlusion, PresigmaST had fallen to 77.4 plus or minus 6.6% of its value 15 minutes postocclusion. In seven experimental dogs, two branches of the LAD were occluded. Fifteen minutes after double occlusion, one occlusion was released; 30 min after the initial occlusion PresigmaST had fallen significantly more than control, to 43.1 plus or minus 13.1% of its value 15 minutes postocclusion. Simultaneously, epicardial sites in the reperfused area also showed normalization of ST segments and 24 hours later exhibited normal myocardial creatine phosphokinase activity and normal histologic appearance. During the same experiment, the mean  precordial R wave voltage of sites with ST-segment elevations exceeding 0.15 mV 15 minutes following occlusion fell significantly (P less than 0.05) more in the control group (from 1.14 plus or minus 0.15 to 0.75 plus or minus 0.06 mV) than in the reperfused group (from 1.06 plus or minus 0.09 to 0.96 plus or minus 0.17 mV) during the ensuing 45 minutes. Thus, more rapid normalization of PresigmaST or preservation of precordial R wave voltage reflected the actual prevention of myocardial necrosis by reperfusion. These findings demonstrate the usefulness of precordial electrocardiographic mapping for evaluation changes in myocardial ischemic injury. Sites at which appearance of epicardial ST segment is not a reliable index of ischemic injury were associated with the development of intraventricular conduction blocks with Q to intrinsic deflection intervals exceeding 40 mesc or QRS durations exceeding 65 msec; these changes were associated with precordial RSR' configurations. Such sites, whether recorded from precordial or epicardial leads, should be excluded from ST-segment measurements used in the assessment of myocardial ischemia.


Digitalis and the sick sinus syndrome. Clinical and electrophysiologic documentation of severe toxic effect on sinus node function. Digoxin, in a common clinical dose and at a low serum level, brought out severe manifestations of sinus node dysfunction in a patient who had previously undergone successful mitral valve replacement. This report presents the results of extensive clinical and electrophysiologic studies of this patient before and after a digoxin challenge. In the absence of cardiac glycoside, the only demonstrable abnormalities of sinus node function were mild resting sinus bradycardia and failure to respond to atropine administration. Responses to isoproterenol administration, programmed premature atrial stimulation, and overdrive pacing at several cycle lengths were normal. Following the administration of intravenous digoxin, 1.025 mg/24 hrs, the resting sinus cycle length increased and the response to overdrive pacing became markedly abnormal. The latter was followed by sinus pauses in excess of six seconds, even at relatively slow overdrive pacing rates. The electrophysiologic and clinical implications of these data are discussed. It is suggested that despite previous reports that digitalis preparations are relatively well tolerated by patients with sick sinus syndrome, caution should be used when administering these drugs to this group of patients.


Coronary ostial stenosis.

Coronary ostial stenosis. Symptomatic, nonsyphilitic, acquired coronary ostial stenosis is a rare angiographic finding and was found in 0.13% of 3000 coronary angiograms. Three females with this lesion have been treated surgically. Two had left coronary ostial involvement. Coronary angiography may result in catheter tip occulsion of the ostium with chest pain, dyspnea, diaphoresis, systemic hypotension and abrupt fall in pressure at the catheter tip. Recognition of this entity is necessary for safe coronary angiography. Involvement of the left ostium carries the same serious prognosis as does left main coronary disease.


The role of an accessory atrioventricular pathway in reciprocal tachycardia. Observations in patients with and without the Wolff-Parkinson-White syndrome. To study the pathway of tachycardia in patients with the Wolff-Parkinson-White (WPW) syndrome and reciprocal tachycardias, results from intracavitary recordings and atrial and ventricular stimulation were reviewed in 71 patients with the WPW syndrome and 54 patients without pre-excitation. In all patients a reproducible tachycardia could be initated and terminated by appropriately timed electrical stimuli. The following findings were accepted as suggesting the participation of an accessory pathway in the tachycardia circuit: 1) no increase in ventriculo-atrial conduction (V-A C) time following ventricular stimuli given with increasing prematurity; 2) activation of right or left atrium (depending upon the location of the atrial end of the accessory pathway) prior to activation of atrium in the His bundle lead; 3) slowing of tachycardia following bundle branch block to the ventricle in which the accessory pathway inserts; 4) V-A C time of early stimuli on the ventricle during the tachycardia equal to or less than the V-A c time following QRS complexes during tachycardia; 5) inability to initiate tachycardia or slowing of tachycardia following the administration of drugs affecting the accessory pathway. Accepted as suggestive for atrioventricular (A-V) nodal re-entry were the following factors: 1) activation of atrium following initiation of tachycardia by a single atrial premature beat after activation of the bundle of His but before or simultaneous with ventricular activation in first and subsequent beats of tachycardia; 2) initiation of tachycardia following a gradual increase in V-A C time with the appearance of a His bundle electrogram in between the premature beat and retrograde atrial activation; 3) gradual increase in V-A C time with the appearance of a His bundle electrogram following ventricular premature beats given with increasing prematurity; 4) two-to-one block distal to the A-V node or His bundle with persistance of tachycardia. If only positive findings were accepted, 51 patients of the WPW group used their accessory pathway during tachycardia. In eight patients re-entry was confined to the A-V node. In the remaining 12 patients the mechanism was not clear. Of the patients not showing pre-excitation in A-V direction, 47 patients seemed to have their re-entry circuit in the A-V node, five patients used an accessory pathway in V-A direction, and in two patients the pathway of tachycardia could not be identified.


Arrhythmias in patients with mitral valve prolapse. Resting ECGs, exercise treadmill tests and 24-hour ambulatory ECGs were recorded and analyzed in 24 unselected patients with mitral valve prolapse. Arrhythmias were frequent. There were three distinct groups of patients, defined on the basis of total number of premature ventricular contractions (PVCs) during the 24 hours; there were no PVCs in 25%, and frequent PVCs in 50%. Complex ventricular arrhythmias, including ventricular tachycardia in five patients, were found almost exclusively in the group with frequent PVCs. Fifteen of the 24 patients demonstrated atrial premature contractions (APCs) during the 24 hours. Complex atrial arrhythmias were found among patients with infrequent, as well as those with frequent, APCs. Supraventricular tachycardia was detected in seven of these patients. The incidence of ACPs decreased during sleep in 67% of the patients and showed no change during sleep in 33%. A poor correlation was found between symptoms recorded in patient diaries and changes noted on 24-hour ECG recordings. The peak PVCs/15 min and peak ACPs/15 min during a 24-hour period of monitoring was found to be an excellent guide to the total number of PVCs and APCs occurring during that period. This permits an accurate prediction of the total number of PVCs in 24 hours after performing an exact PVC count on only 15 minutes of ECG data. Finally, the 24-hour ambulatory ECG was sensitive than the treadmill test and both were superior to the 12-lead ECG for detecting arrhythmias in these patients.


Surgical bifascicular block.

Surgical bifascicular block. Electrophysiological studies were performed in 18 patients who developed bifascicular block after repair of ventricular septal defect (VSD) or tetralogy of Fallot (TF). Two had transient complete heart block (CHB) in the immediate postoperative period. The P-A intervals were normal in all. A-H and H-V intervals were prolonged in three and four cases, respectively. Atrial pacing at progressively increasing heart rates was performed in 15 patients; two developed type II block distal to the His bundle (H). The effective and functional refractory periods (ERP and FRP) of the atrium (11 cases) were normal in all. The ERP of the A-V node (seven cases) was prolonged in found and the FRP was increased in three. The ERP of the ventricular specialized conduction system was measured in two cases and was prolonged in one. In all, seven cases had abnormalities indicating disease of the A-V node and/or His-Purkinje system. Recording of intervals, atrial pacing, and determination of refractory periods (RPs) was necessary to reveal all conduction abnormalities. One patient died of unrelated causes. The others are alive and in sinus rhythm with intact conduction 3 to 16.5 years following surgery (mean follow-up of 8.3 plus or minus 0.95 years). The clinical course in patients with normal and abnormal findings was equally benign. Prophylactic insertion of demand pacemakers does not appear indicated in these patients.


The scope of mass spectrometry in clinical chemistry. Several aspects of mass spectrometry and gas chromatography-mass spectrometry are reviewed, including ionization methods, repetitive scanning, selected ion monitoring, and stable isotope measurement. I discuss the application of these and other mass spectrometry methods to the investigation of compound classes relevant to clinical chemistry, to the assessment of inborn errors of metabolism, and to clinical studies. The latter include consideration of volatiles in body fluids, respiration and blood gases, stable-isotope applications, clinical toxicology, and drugs.


Citrate synthesis by lymphocytes.

Citrate synthesis by lymphocytes. The important role of lymphocytes in humoral and cell-mediated immunity indicates that they need a readily available intracellular source of energy. Here, we demonstrate that these cells contain enzymes involved in citrate formation. The citrate is oxidized through the tricarboxylic acid cycle to furnish energy. A newly devised, simple radiometric method was used to determine the condensation of labeled acetate or acetyl CoA with oxaloacetate to form citrate. The de novo synthesized citrate was oxidized to pentabromoacetone, and radioactivity of the resulting CO2 was directly related to the amount of citrate synthesized. Both lymphocytes from chronic lymphatic leukemia patients and cultured lymphoblasts possess this active citrate-synthesizing apparatus, although the lymphoblasts appeared to have a considerably higher activity, perhaps because they are larger.


Computer-controlled automation of radioimmunoassay based on gel entrapment of antibody. We describe a new, broadly applicable approach to radioimmunoassay. Solid-phase binding reagent is prepared by entrapping antibody in polyacrylamide gel. This gel is then fragmented, sieved, and dehydrated in 95 percent ethanol. Upon evaporation of the ethanol, the dry antibody-gel particles are dispensed into miniature disposable plastic columns. A unidirectional flowing stream configuration is used to construct a standard curve for the polypeptide hormone, angiotensin I, used here to exemplify the technique. Good reproducibility of this standard curve is demonstrated. The analytical system includes a computer-controlled sample turntable, digital pipet, and liquid-switching assembly.


Rapid analysis for theophylline in serum by use of high-pressure cation-exchange chromatography. We have developed a quantitative assay for serum theophylline by high-pressure cation-exchange chromatography. As little as 0.1-ml aliquots of serum were prepared for analysis simply by diluting them with a solution of the internal standard (8-chlorotheophylline). Theophylline and the internal standard were eluted in 17 and 27.5 min, respectively, and the peaks for them were distinct from those of other xanthines and uric acids. We encountered no interference when we used: (a) plasma obtained from blood anticoagulated with citrate; (b) hemolyzed, lipemic, or icteric serum; or (c) 52 samples from patients who were receiving various other medications. An analysis of calibration suggested that errors greater than plus or minus 2.6 mg/liter, a clinically acceptable range, were highly unlikely. Sensitivity was sufficient to identify less than 2.5 mg/liter. This assay was compared with the usual method involving solvent extraction and absorbance measurement in the ultraviolet and found to have similar accuracy, although it is easier, faster, requires less sample, and potentially is more specific.


Gas-liquid chromatographic measurement of guanidino acids. We present a method for separating and measuring guanidino acids by gas-liquid chromatography. Compared to ion-exchange techniques, this system is faster, more sensitive, requires smaller sample volumes, is independent of colorimetric reactions, and permits simultaneous determination of both amino and guanidino acids. N-Trifluoracetyl-n-butyl esters are formed and then are separated by using a column containing a mixed silicone liquid phase coated on Chromosorb W-HP. Analytical recoveries from plasma ranged from 86 to 112% and were done without prior protein precipitation. Speculations as to the cause of this interference by protein include coprecipitation, protein-binding, and cyclization of the guanidines in the acids used for denaturation. Evidence presented suggests that all three occur: ultrafiltrability is diminished in the presence of protein and nuclear magnetic resonance demonstrates cyclization of some of these esters.


Rapid separation of plasma creatine kinase isoenzymes by batch adsorption on glass beads. To separate the MM and MB creatine kinase (EC 2.7.3.2) isoenzymes in small plasma samples, we developed a simple, rapid ion-exchange batch-adsorption procedure with "DEAE Glycophase" glass beads (Corning). All separative steps are performed in a single test tube and can be completed within a few minutes. Results of measurements of isoenzymes in plasma samples from patients with acute myocardial infarction were compared to those obtained with an independent quantitative assay method previously reported. Additional measurements were performed on standard plasma samples containing mixtures of MM and MB isoenzyme purified from human myocardium. Results by the two independent assay procedures agreed well, as did measured isoenzyme activities and activities predicted from the amounts of isoenzyme added. Activities in the fractions containing separated isoenzymes were measured by a direct kinetic fluorometric assay. MB activities in normal plasma averaged 1.6 plus and minus 0.28 U/liter (mean plus and minus SD).


Evaluation of the revised serum calcium procedure used with the Du Pont automatic clinical analyzer. We evaluated a revised serum calcium method (o-cresolphthalein complexone) used with the Du Pont aca. Our results correlated well with those obtained by atomic absorption spectrometry. Within-run and day-to-day coefficients of variation were 0.5 and 1.5%, respectively. Color produced and calcium concentration are linearly related and the relation is not affected by hemolysis, lipemia, or icterus.


Direct method for measuring lipoprotein-X in serum. We describe a fast and easy method for routine quantitation of the abnormal lipoprotein, lipoprotein-X. The procedure is based on densitometry of precipitation areas obtained for it after serum electrophoresis in agar gel followed by precipitation with polyanions. The coefficient of variation was less than 3% in one series. Results were linearly related to concentration in the range 0.063 to 6.3 g/liter.


Use of high-resolution open tubular glass capillary columns to separate acidic metabolites in urine. We used high-resolution glass capillary columns to study the trimethylsilyl derivatives of some acidic metabolites found in pooled urine specimens form control and postpartum subjects. About 30 compounds were identified by gas chromatography-mass spectrometry-computer techniques. In general, open tubular capillary columns effect better resolution of trimethylsilyl derivatives of organic acids than do conventional packed columns. GESE-30 proved to be a good general-purpose stationary phase, whereas OV-17 offered certain advantages in resolving aromatic acid components.


Correction for spectral interference with determination of lead in blood by non-flame atomic absorption spectrometry. A non-flame atomizer incorporating a graphite tube and cup is used to determine lead in whole blood and packed erythrocytes. In a direct method, a 2-mu-l sample is treated in situ in the cup with 1 mu-l of concentrated nitric acid. The oxidized sample can then be dried, ashed, and atomized without leaving a residue. The nitric acid treatment obviates correction for nonselective absorption, something previously necessary in the determination of lead in blood by non-flame techniques. The resulting chemical conversion of the matrix compounds frees the lead atomic absorption peak from the spectral interference. Alternatively, a 50-mu-l sample of blood or erythrocytes is treated with 50 mu-l of concentrated nitric acid and a 1.5-mu-l aliquot is analyzed with use of the graphite tube.


Rate of decrease in serum ethchlorvynol concentrations after extreme overdosage-a case study. Ethchlorvynol is a commonly abused sedative hypnotic. I report here a seven-day study of serum ethchlorvynol concentrations in a patient who had received an extreme overdose. These concentrations were correlated with the patient's response to stimuli. Serum ethchlorvynol concentrations were logarithmically related to time, a fact that can be useful in predicting when a patient's serum ethchlorvynol concentration will return to a therapeutic concentration. In this case the decrease was about 35% per 24h.


Venous serum, capillary serum, and capillary plasma compared for use in determination of lactate dehydrogenase and aspartate aminotransferase activities. Lactate dehydrogenase and aspartate aminotransferase activities in capillary serum or plasma were significantly greater than in simultaneously assayed venous serum, the greatest differences being between capillary and venous serum. Although some difference is attributable to tissue fluid contributions, platelets seem to account for most of it, with possible small contributions from leukocytes. Capillary tube size and type appear to be important factors. We recommend that when capillary blood is to be used for enzyme assay, it should be processed as plasma.


Inhibitory effect of fluoride on glucose tests with glucose oxidase strips. Sodium fluoride was inadvertently added as a preservative to the urine of an eight-year-old boy with diabetes mellitus before urinary glucose was measured. On preliminary screening of the urine, the test by glucose oxidase paper reagent strip gave a negative reading for glucose, whereas quantitative urinary glucose assay by the coupled enzyme reaction (hexokinase-glucose 6-phosphate dehydrogenase) gave a glucose concentration of 81.5 g/liter. Inadvertent use of sodium fluoride as a urine preservative may cause a falsely negative result with the glucose tests involving oxidase.


A new convenient, rapid and accurate method for determination of total lipids in feces. 1. A new, simple and rapid colorimetric micromethod for determination of total lipids in the petroleum ether extract of feces is proposed. The method, based on the sulfophosphovanillin reaction, was found to be of satisfactory precision and accuracy. 2. The concentration of total lipids determined in meconium of 40 healthy newborns in the first five days of life, was 1 to 15 g/100 ml of feces.


Studies on non-haemoglobin erythrocyte iron; the influence of haemolysis on plasma iron determinations. Approximately 2% of iron contained in mouse erythrocytes is transferred into supernatant when haemolysed erythrocytes are precipitated with trichloroacetic acid. The component unprecipitable with trichloroacetic acid is probably bound predominantly to reticulocytes and it is larger the younger is the reticulocyte. Under the conditions of postirradiation suppression of erythropoiesis this component grows strongly and in the phase of overrecovery of erythropoiesis decreases. The numerical values determined in the paper can be used for a correction of the disturbing influence of haemolysis on concentration and radioactivity of plasma iron in the resting state of erythropoiesis, if a preliminary precipitation of a sample with trichloroacetic acid was carried out.


Comparison of the chemical composition of glomerular and tubular basement membranes obtained from human kidneys of diabetics and non-diabetics. Glomerular basement membrane (GBM) and tubular basement membrane (TBM) were prepared from human kidneys of diabetics and non-diabetics, and their chemical composition was compared. GBM from diabetics contained a larger amount of hydroxyproline than that from non-diabetics, and smaller amounts of half-cystine, glucose, mannose and sialic acid. On the other hand, TBM from diabetics contained larger amounts of hydroxylysine, methionine, galactose, hexosamine and phospholipid phosphorus than non-diabetics, and smaller amounts of half-cystine, valine, leucine, lysine and histidine. No significant difference was observed in the contents of other components examined in this study between the corresponding membrane obtained from diabetics and non-diabetics. The observed changes may be due to alteration of the tissues in diabetes mellitus.


Vitamin B-1, B-2 and B-6 deficiencies in geriatric patients, measured by coenzyme stimulation of enzyme activities. The vitamin B-1, B-2 and B-6 nutritional status of 153 geriatric patients was determined by measurement of the activities of transketolase (TK), glutathione reductase (GR) and glutamic-oxaloacetic transaminase (GOT) from hemolyzed erythrocytes before and after in vitro stimulation with their respective coenzymes. The change in enzyme activity after incubation of the hemolysate with the coenzyme was used to determine the activation coefficient, which was taken as an index for the vitamin B-1, B-2 and B-6 nutritional status. Determination of the normal values in 54 healthy blood donors showed that activation coefficients of TK greater than 1.27 indicated a biochemical vitamin B-1 deficiency. Activation coefficients of GR greater than 1.29 and GOT greater than 1.86 indicated, respectively, deficiencies of vitamins B-2 and B-6. On the basis of these findings 22.9% of the geriatric patients appeared to suffer from vitamin B-1 deficiency, 11.7% from vitamin B-2 deficiency and 19.0% from vitamin B-6 deficiency. Of the total number of patients, 44% showed a deficiency of one or more of these three vitamins. Oral administration of vitamin B-1 (20 mg/day), vitamin B-2 (10 mg/day) and vitamin B-6 (20 mg/day) for twelve days normalized nearly all activation coefficients. Determination of enzyme activities without coenzyme stimulation revealed significantly lower values in the deficient patients as compared with the blood donors. However, the distribution of activities for both groups overlapped to a great extent. Oral administration of vitamins raised the enzyme activities to normal values.


[Changes of blood-flow properties in patients with chronic liver disease (author's transl)]. The determination of plasma viscosity in 37 patients with liver disease allowed their subdivision into three groups. Firstly, decreased viscosity (hypoviscosity) was found in patients with cirrhosis, marked portal hypertension and esophageal varices. Secondly, normal viscosity (normoviscosity) was found in patients with inactive cirrhosis without portal hypertension, and thirdly, increased viscosity (hyperviscosity) was found in patients with active cirrhosis and chronic progressive hepatitis. The concentrations of total serum protein, of fibrinogen and of IgG were found to influence plasma viscosity. A detailed differentiation revealed that increased plasma viscosity is caused by increased levels of IgG while decreased viscosity correlates with low fibrinogen levels. Furthermore a close correlation exists between plasma viscosity and the enzymatic activity of SGOT, SGPT and GLDH. In 5 patients with chronic progressive hepatitis treated with corticosteroids the plasma viscosity normalized in parallel with improvement of the hepato-cellular damage. These findings will be discussed in detail. Hyperviscosity might possibly serve as an additional parameter to characterize chronic progressive hepatitis and to indicate steroid treatment.


Glucose consumption by red cells of diabetic patients and normal subjects. Effect of ethanol. Glucose consumption was measured in the red cells of 15 diabetic patients and 13 normal subjects. The red cells were incubated in autologous serum with the glucose concentration adjusted to approximately 500 mg per 100 ml. Mean glucose consumption, both total and via the pentose phosphate pathway, by the red cells of the diabetic patients was not significantly different from that by the red cells of the normal subjects. Stimulation of the pentose phosphate pathway with ascorbate or methylene blue similarly revealed no difference between the two groups. Exposure of the red cells to ethanol in the incubation medium had no discernible effect on total glucose consumption but caused a decrease in glucose consumption by the pentose phosphate pathway. An effect of ethanol on glucose consumption by the pentose phosphate pathway was not evident in the presence of ascorbate or methylene blue. No difference in response to ethanol by the red cells of the diabetic patients and normal subjects was observed.


Some properties of alkaline-phosphatases in parenchymal and biliary tract cells separated from rat liver. Livers of both normal and bile-duct ligated rats have been separated into parenchymal cells and fractions enriched in biliary tract cells. The specific activity of alkaline phosphatase increases in both types of cells after occlusion of the bile duct but the increase is more marked in the case of parenchymal cells. The enzyme from parenchymal cells migrates as a single zone on electrophoresis, whereas additional zones of lower anodal mobility occur in extracts of biliary tract preparations. The alkaline phosphatase activity of the slower zones is significantly less stable to heat than that of the zone characteristic of parenchymal cells. It is postulated that the increase in heat stability of alkaline phosphate in extracts of whole rat liver after bile-duct ligation is due to an increase in the proportion of the more stable form of the enzyme predominant in parenchymal cells.


An improved radioimmunoassay of serum gastrin using commercial kit. Our experience with a commercially available kit for the measurement of serum gastrin has been reported. Significant non-specific interference was noted by the addition of serum contents in the assay which lead to erroneous results. Use of gastrin free serum as a diluent in the standard curve was found to improve the mean recovery of added gastrin. With this modification the procedure was evaluated for its clinical application. In 30 normal subjects, the fasting mean gastrin level was 78.7 plus or minus 31.9 (S.D.) pg/ml; in 18 of these individuals the postprandial mean level was 118.3 plus or minus 26.7 (S.D.) pg/ml. In 15 patients with pernicious anemia the mean level was 912 plus or minus 779 pg/ml; and in 4 patients with Zollinger-Ellison (ZE) syndrome the mean gastrin level was 1950 plus or minus 379 (S.D.) pg/ml. A significant rise in gastrin level was noted in patients with kidney failure during and after dialysis (p smaller than 0.05).


Zinc and copper urinary excretions in children with burns and scalds. The daily urinary losses of zinc and copper have been measured over periods of up to 12 days following thermal injury in 18 children. Comparison with measurements of zinc and copper excretions in 35 control children showed that after injury by burning or scalding, the urinary excretions of both metals were increased in many of the patients. After severe injury, high urinary outputs of zinc and copper persisted for up to two months following injury.


Plasma amino acids and protein levels in chronic renal failure and changes caused by oral supplements of essential amino acids. 1. Plasma amino acids and six proteins have been measured in patients with chronic renal failure receiving low protein diets before and after oral supplementation with essential amino acids. 2. All the patients on low protein diets had a lower percentage of essential amino acids in their plasma than normal subjects but after supplementation, plasma levels increased significantly with minimal increase in non-essential amino acids or urea nitrogen. 3. Mean levels of plasma transferrin, complement C3 and globulin Gc were lower and plasma prealbumin higher in patients than in normal subjects. Plasma complement C4 and albumin were not different from normal. 4. Seven out of nine patients who tolerated the supplementation showed a significant increase in plasma transferrin, prealbumin and complement C3 but not in complement C4, globulin Gc or albumin. 5. Correlations between the percentage of essential amino acids and each of plasma transferrin, prealbumin and complement C3 and also between several of the plasma proteins further substantiate their value in the assessment of dietary intake in chronic renal failure. 6. The value of amino acid supplementation on low protein diets in chronic renal failure is discussed in relation to these observations.


Plasma carnosinase deficiency in patients with urea cycle defects. A complete absence of plasma carnosinase activity was observed in a series of patients with proven urea cycle defects. This finding could not be explained by age of patients, low protein intake, or inhibition of the enzyme by glutamine or carbamyl phosphate.


Adrenocortical response during examination. The stressful effect of a written and oral examination was studied in twenty-two doctors sitting a postgraduate examination. The rise in the plasma cortisol was not significant in the written examination and reverted to normal values  after an hour. On the other hand, there was a significant rise in the plasma cortisol during the oral examination with a pre-entry rise in blood sugar and a fall in alpha-amino nitrogen. It is concluded that whereas a written examination is not a stressful situation, an oral examination is stressful enough to be comparable to rowing and flying.


Incontinentia pigmenti.

Incontinentia pigmenti. Four new cases of incontinentia pigmenti are presented, including chromosome studies of one family. An increased number of chromosome breakages was found in the blood of affected as well as unaffected members of this family.


A new form of hereditary short limbed dwarfism with microcephalus. Siblings, one female and one male, were each born approximately 1 month prematurely and showed microcephalus, shortness, and short limbs plus a receding forehead and one peculiarly positioned small toe. Each failed to thrive, and neither made any developmental progress beyond the newborn status. Each exhibited a similar leukemoid reaction, and one died of respiratory infection at 3 months, the other of seizures and central nervous system infection at 5 months. At autopsy, each had a small brain, hydrocephalus, and bony anomaly of the cranium, the one of the posterior fossa and the other of the foramen magnum; in addition, one had absence of the corpus callosum. The long bones were considered atypical of chondrodystrophy. The combination of midly shortened bones of the extremities, moderately anomalous ribs, and slightly flattened vertebrae with microcrania does not resemble any of the previously recognized forms of short limbed dwarfism. We propose determination by a single, rare, autosomal recessive gene. The parents had greatly different ancestry and their apparent heterozygosity for such a gene made their mating particularly unusual.


A familial F/G translocation [t(p-; 22q+)] observed in three generations. A family is described in which a translocation between chromosomes 20 and 22 has been observed in three generations. Two first cousins with remarkably similar malformations and mental retardation have identical karyotypes which, after chromosome banding, were interpreted as partially trisomic for the short arm of chromosome No. 20.


Cystic fibrosis heterozygote detection: a study on a normal population. Detection of the cystic fibrosis (CF) heterozygote by testing for cystic fibrosis factor activity (CFFA) in serum samples using bioassays had been reported to give unreliable results. The present study was undertaken to find whether the use of medium from short term white blood cell or skin fibroblast cultures, rather than serum, as the test sample would eliminate such inconsistencies. Short term white blood cell cultures were established from 107 normal, healthy individuals. Cultures from 97 had no CFFA, six (No. 1-6) showed variable results and four (No. 7-10) had activity in all four tests done on a single sample. When the assays were repeated 3 months later on new cultures from these four positive CFFA individuals, two showed activity (Nos. 7 & 9) and two did not (Nos. 8 & 10). All 10 individuals whose cultures showed CFFA has histories of allergies. The association of CFFA in the culture medium derived from individuals having allergies with the intermittent presence of this activity suggested that environmental factors induced a CFF-like activity in such white blood cell cultures. The oyster ciliary assay, using medium from white blood cell cultures, cannot be used for screening for the CF heterozygote since the substitution of culture medium for serum did not eliminate inconsistent results and CFFA was not specific by this assay for the CF gene. Of the fibroblast lines established from the four persons whose initial white blood cell cultures consistently showed CFFA, only one (No. 7) showed the CF culture phenotype (CFFA positive and metachromasia).


A new case of the trisomy 9P syndrome. Report of a patient with unusual chromosome findings (46,XX/47,XX, +  i (9p) and a peculiar congenital heart defect. A girl is described for whom an unusual chromosome constitution was found and who had a peculiar congenital heart defect. The girl showed the main clinical features of the trisomy 9p syndrome, such as psychomotor retardation, microcephaly and brachycephaly, enophthalmos, antimongoloid eye slant, hypertelorism, abnormal ears, a globulous nose, downward slanting mouth, hypoplasia of phalanges and abnormal palmar creases. In addition, the girl had an incomplete harelip, a cleft palate and a peculiar congenital heart defect, a ventricular septal defect with pulmonary valve stenosis and a marked hypoplasia of the pulmonary trunk, including the bifurcation. Chromosome analysis revealed a mosaicism with normal and abnormal mitoses (47 chromosomes). The extra chromosome was a metacentric E16-like chromosome, which on the basis of the G, R, Q and Giemsa-11-banding could be identified as an isochromosome of the short arm of chromosome 9 (46,XX/47,XX, +i (9) (pter leads to cen leads to pter)). The patient consequently had a partial tetrasomy of the short arm of chromosome 9.


Familial primary vesicoureteral reflux.

Familial primary vesicoureteral reflux. Two families with all children affected by primary vesicoureteral reflux are reported. Both sets of parents were examined and only in one family the mother was also affected by unilateral reflux. This congenital lesion has only recently been recognized  as a common disease, but because diagnosis depends on voiding cystography, it is not made until the child or adult becomes symptomatic or presents with end-stage renal disease. As most cases are sporadic, a multiple factorial mode of inheritance is most probable, but an autosomal dominant or recessive gene cannot be excluded as the cause of the disease in some families. It is recommended that all first degree relatives of the patients should be investigated, in order to detect asymptomatic cases of this condition, which is likely to cause progressive renal damage and may have fatal termination due to renal failure.


Isochromosome for the short arm of X: a human mosaic 45,x/46,XXpi. An 18 year female patient with short stature, amenorrhoea and poorly developed secondary sexual characteristics, has subnormal oestrogen excretion and increased levels of plasma gonadotrophin. Laparoscopy revealed streak ovaries. A reduced number of buccal mucosal cells showed positive sex chromatin. Chromosome studies of blood lymphocytes indicated mosaicism: the major cell line was characterized by an isochromosome for the X short arm, 46,XXpi; the minor cell line had a single X chromosome, 45,X.


An XX male: cytogenetic and endocrine studies. A 3 year old black male with ambiguous genitalia had a 46, XY karyotype in a bone marrow culture and an intermediate buccal smear result, suggestive of a mosaic of chromatin positive and chromatin negative cells. Upon re-evaluation at age 15 years, he has a 30% positive buccal smear and a 46, XX karyotype in cultures of peripheral blood lymphocytes, skin fibroblasts, bone marrow, and testis. No Y-body fluorescence was detectable in interphase cells from the testicular biopsy or the various cultures. The testicular biopsy appeared similar to that of XXY males, and primary hypogonadism was documented by elevated LH (107 mIU/ml) and FSH (57 mIU/ml) levels in conjunction with low testosterone (142 ng/100 ml). Administration of hCG produced qualitatively normal acute responses of testosterone and estrogens. The cytogenetic data provide support for the theory that at least some XX males once had a Y-containing cell line which was subsequently lost.


A possible major contribution to mental retardation in the general population by the gene for microcephaly. In a study of 13 families with genetic microcephaly, it was found that 11 of 24 parents (two fathers not ascertained) and 11 of 33 non-microcephalic siblings were of subnormal intelligence. In a rare autosomal recessive condition, all parents and two-thirds of unaffected siblings are presumed carriers of the gene. It so, nearly 50% of all presumed heterozygotes in the present study were mentally retarded. The proportion agrees well with the other major study of microcephaly in North America, but differs from the Dutch study. On the basis of pooled data from the three studies and the estimated incidence of 1:40000 for genetic microcephaly, it is postulated that (1) about 0.34% of the general population is mentally retarded because it is carrying the gene for microcephaly and (2) about one of nine mentally retarded individuals is heterozygous for the gene for microcephaly.


Familial D/D translocation t(13q;14q). Eight members in four generations. Eight family members spanning four generations were found to have 45 chromosome count D/D trnaslocation identified by Giemsa-trypsin banding as t(13q;14q). The only mature male is believed to be infertile on the basis of a very low sperm count with reduced motility. This is believed to be related to the chromosome aberration and not to be coincidental. Aside from this, all were clinically normal except the index case, a young girl with unusual facies and moderate to severe retardation of growth and development. It is believed that her abnormalities were coincidental to the chromosome translocation and fortuitous in locating this family and initiating the pedigree. This example of essentially benign (some males are fertile) Robertsonian centric fusion in humans lends itself to interesting speculations about the results from chance matings between such translocation carriers.


Genetics of acheiropodia (the handless and footless families of Brazil). The acheiropodia data are shown to be consistent with the hypothesis of a fully penetrant gene in the homozygous state. The expressivity is shown to be generally constant, with some minor variation between individuals as well as between the two sides of the same affected person.


Scanning and angiography in the diagnosis of pulmonary embolism. Lung scanning is a safe and simple procedure which, when correlated with chest roentgenograms and clinical picture, is a valuable tool in diagnosing pulmonary embolism. Pulmonary arteriography is a valuable diagnostic procedure and should be employed when serious doubt exists as to the presence or absence of pulmonary emboli. It should also be used whenever surgical treatment is under consideration.


An evaluation of cervical and lumbar discography. Discography as a diagnostic method is not a panacea and has distinct limitations. It should not replace myelography but is a useful adjunct, particularly in those cases in which myelography has not been helpful and in which conservative management has failed to produce improvement. It is particularly helpful in determining the level of fusion and selection of patients with cervical disks that need to be fused.


The use of tomography in the diagnosis of skeletal disorders. Tomography has definite proven value as a technique in studying objects obscured by overlying shadows. It is an adjunct study to conventional radiographs when the necessary detail for diagnosis is lacking in the routine examination. Particularly in skeletal tumors, tomography can be helpful in disclosing lesions too small to be noticed in the routine radiograph or resolve details in question in the conventional film that are pertinent to the diagnosis. This technique has also been of great benefit in detailing the anatomic structures of the spine, temporomandibular joints and sternoclavicular articulations. It has been of particular value in the evaluation of fracture-healing or the presence of pseudarthrosis and arthritis affecting the larger joints of the body.


Fluoride-18 scintigraphy in avascular necrotic disorders of bone. Fluoride-18 scintigraphy is a simple, safe method for evaluating perfusion to bone, and obviates objections to earlier techniques. The scintillation camera with positron detection represents a unique instrumentation system because of its tomographic effect, relative insensitivity to vascular radioactivity in the surrounding skeleton, and excellent spatial resolution despite low counting efficiency. In 75 patients with avascular disorders about the hip, knee, elbow, foot and hand, the impressions obtained from fluoride-18 scintigraphy were correlated with clinical findings and roentgenograms and when possible confirmed by tetracycline labeling and histological examination. Fluoride-18 scintigraphy was useful: in determining the vascularity of the femoral head following femoral neck fractures; in determining results of treatment; and in diagnosing early the various avascular necrotic disorders of the bone.


18-F scintimetric diagnosis of osteoid osteoma of the carpal scaphoid bone. In a patient with symptoms suggestive of osteoid osteoma of the carpal scaphoid, 18-F scintimetry supported the diagnosis in the absence of clear cut roentgenographic signs. High concentration of 18-F in the area of the lesion allowed direct surgical approach and extirpation. The diagnosis was proven by histology.


A single stage osteotomy and epiphysiodesis for treatment of moderately displaced femoral capital epiphyses. Epiphysiodesis and subtrochanteric osteotomy have long been recognized as valuable procedures in the treatment of the patient with a moderately or markedly displaced femoral capital epiphysis. Typically these have been performed individually or sequentially. The operation herein described combines the two in one single-stage procedure. Using a stainless steel Lorenzo Screw, the epiphyseal plate is transfixed and further capital displacement prevented. The subtrochanteric compensatory osteotomy is performed using simple visual clinical guidelines and is held rigidly immobilized with a variable angle sideplate affixed to the Lorenzo Screw. The firm fixation enables one to dispense with plaster immobilization and begin the patient on an early exercise program. Restoration of a more normal range of motion, especially regarding rotation internally, abduction, and flexion is easily obtained. Radiographic correction of varus and posterior tilting are thereby secured.


Epithelioid sarcoma involving bone.

Epithelioid sarcoma involving bone. This is a report of a case of extension of an epithelioid sarcoma into the medullary cavity-a fact that may alter the relatively good prognosis of this entity, and seems not to have been reported previously. It is important to add epithelial sarcoma to the differential diagnosis of tumor masses on the extremities. A cure may be achieved by wide local excision at an early stage of the disease.


Roentgenographic detection of preventable occult pseudarthrosis in treatment of scoliosis. Occut pseudarthrosis is the most likely cause of loss of correction of scoliosis. Prompt detection by serial roentgenograms and treatment of occult pseudarthrosis can prevent deformities which could develop with further spinal growth.


A new patella prosthesis. Design and application. The new patella prosthesis design is based on an anatomical study of 80 arthritic patellas and on the normal patellofemoral contact area under loading in cadaver knees. The metal dome-shaped prosthesis is attached by a central pin. The patellar prosthesis is constructed either of metal or plastic for use in combination with the Hospital for Special Surgery design of total knee prosthesis. Methylmethacrylate is used to supplement the fixation after resection of the abnormal patellar articular surface. The fixation tests gave excellent laboratory results for contact area and stability. The prosthesis has been used in 19 cases with encouraging early results.


Degeneration and rupture of the Achilles tendon. An analysis was perfomed on 32 operative cases of Achilles tendon disease. Two patient classifications emerged. One group suffering an acute rupture of the Achilles tendon with no antecedent complaints, and the second group had a history of chronic pain, weakness and functional loss. This latter group could be further differentiated by the occurrence of tendon failure in 10 of 22 cases. Surgical exploration in the group with chronic complaints demonstrated a high incidence of diffuse reactive changes such as fibrinoid and myxomatous degeneration, fibroisis and metaplastic calcification. Degenerative disease of the Achilles tendon should be recognized and treated not as a simple injury but as a pathological lesion.


The Mitchell distal metatarsal osteotomy in the treatment of hallux valgus. Many of the fair and poor results are directly traceable to errors in technique. Patient selection is also important. The operation can be done in adolescents since there is no growth plate at the distal end of the first metatarsal. We do not currently recommend this procedure for those over 60, for those with first metatarsophalangeal osteoarthritis or hallux rigidus or for those with moderate or severe rheumatoid arthritis. For these patients we usually do a Keller excisional arthroplasty. Our use of the osteotomy-bunionectomy operation for the patient with hallux valgus with an associated metatarsalgia or short first metatarsal has now become more cautious. We feel that the operation is not indicated for those with significant preoperative metatarsalgia, especially if the first metatarsal is shorter than the second, or for those whose first metatarsal is more than 4 or 5 millimeters shorter than the second, regardless of preoperative metatarsalgia. In these patients a McBride procedure or a proximal opening-wedge osteotomy is done.


The effect of growth hormone on established cartilage lesions. A presidential address to the Association of Bone and Joint Surgeons, 1974. The major problem in osteoarthritis research today is our inability to promote effective cartilage regeneration in the presence of adult chondromalacia. Yet such regeneration is consistently present in acromegalics. The present study of experimentally damaged rabbit knee cartilage measures numbers of cells, mitoses, tritiated thymidine incorporation, DNA content, collagen presence under polarized light and sulfated protein polysaccharides histologically. Under growth hormone stimulation cell counts nearly double as compared to controls, TTI increases, DNA content triples or more. Matrix healing is evident histologically. The addition of salicylate has a mild additive effect on cell counts and on retention of matrix. The above data appear to be the first reported demonstration of these effects of growth hormone on experimentally damaged cartilage and may gain importance for clinical use when human growth hormone or substitutes for it become available.


An experimental study of surface injury to articular cartilage and enzyme responses within the joint. An experimental model of degenerative joint disease on chondromalacia consists of a surgically-scarified articular surface of the adult dog knee joint. In 52 dogs, evaluated by histologic and enzymatic assays over a period of 1 to 110 weeks post-surgery, the levels of acid hydrolase activity varied on various areas of articular cartilage within the same joint. There was a transient rise in most of the acid hydrolases in the synovium as a response to arthrotomy of the knee joint. All of the acid hydrolases studied did not respond uniformly to surgically created trauma. There was evidence of repair of the cartilage lacerations even when the subchondral zone was not breached. Lacerations in the central portion of the patella rarely showed healing in contrast to those placed more to the periphery of the articular surface. There was no gross or histologic evidence of progressive degenerative joint disease up to 2 years post-surgery. Thus an injury inflicted to the surface of the articular cartilage may be in itself insufficient in severity to produce destructive changes in the joint. This should not be too surprising, since, clinically, all joint surface injury does not lead to degenerative arthritis. The joint seems to have an injury threshold whereby chondrocytes are capable of repairing surface injury if the damage is not massive or repetitive. Insofar as lacerations in the center of the patella rarely healed, while the peripheral ones showed consistent signs of healing, the site of injury, as well as the magnitude of injury, may be critical.


The biochemical activity of fracture callus in relation to bone production. Quantitative microchemical study of the tissues comprising fracture callus has been undertaken to correlate the biochemical activity of the bone repair process with its previously established morphological features. Areas of proliferating fibrous tissue, hypertrophic cartilage, new bone and undifferentiated granulation tissue were analyzed for their content of carbohydrate metabolizing and phosphatase enzymes. Fracture callus cartilage is biochemically similar to epiphyseal cartilage. Carbohydrate metabolism provides structural intermediates and energy for bone repair. Inorganic pyrophosphatase removes the inorganic pyrophosphate which accumulates from structural synthesis and prevents its inhibition of new bone calcification. The individual parts of the callus have identical biochemical function regardless of the age or healing time of the fracture callus.


Circulatory depression in bone after acrylic implantation. Because of the continuing hazard of post-operative sepsis in joint replacement surgery and the possibility that persistent bone ischemia may be a contributing factor, it is desirable to know the hemodynamic consequences in bone of the implantation of orthopedic acrylic cement. Experiments were carried out on 60 rats. In 30, a bore-hole was made, unilaterally, in the tibia. In another 30, a bore-hole was made in the tibia and a small amount of polymethylmethacrylate cement (Surgical Simplex P) was implanted into the marrow cavity through the bore-hole. By means of 51-Cr labeled red cells and 59-Fe labeled resin particles, the blood volume and blood flow rate in the tibiae were calculated simultaneously as a percentage of the values in the contralateral tibiae. The results showed that at 14 days and 112 days postoperatively, both blood volume and flow were significantly depressed in tibiae in which acrylic cement had been implanted, as compared with tibiae in which only a bore-hole had been made. It was concluded that orthopedic cement implanted into bone renders the bone hypovascular.


Ultrastructure of a mixed form of calcinosis. An unusual form of calcinosis is described presenting a joint occurrence of calcinosis circumscripta and calcinosis universalis. Ultrastructurally, the mineral constituent is of much higher crystallinity than that of normal bone, and includes a rare kind of carbonate apatite. The crystals of the specimen were needle-like and hexagonal, in juxtaposition to normal collagen fibrils. Supposedly, the development of the calcifiable matrix is different in calcinosis and bone tissue.