An unusual effect of N-octylamine on the cytochrome b5 spectrum of insect and mammalian microsomes.

The addition of n-octylamine to microsomes prepared from the midgut of tobacco hornworn (Manduca sexta) larvae causes an unusual spectral interaction. The initial optical difference spectrum appears to be the sum of reduced cytochrome b5 and a type II difference spectrum of cytochrome P-450. This initial spectrum is unstable and diminishes in size, with a concurrent shift in peak (424 to 428 nm) and trough (409 and 392 to approx. 400 nm) positions, to yield a stable spectrum identical to the type II spectrum of cytochrome P-450. Thus, in addition to its interaction with cytochrome P-450, n-octylamine causes a reduction of cytochrome b5 which subsequently becomes reoxidized. The causal factor for this unusual spectral interaction occurs in the cytoplasm and appears to be protein-bound. It was also present in similar preparations from the tobacco budworm (Heliothis virescens) but not in those from rat or mouse liver or abdomens from insecticide-resistant or susceptible houseflies (Musca domestica). Microsomes from rat and mouse liver, but not those from housefly abdomens, exhibit similar unusual spectral interactions with n-octylamine when supplemented with the soluble factor from the hornworm.


The effect of vinyl chloride monomer, chloroethylene oxide and chloracetaldehyde on DNA synthesis in regenerating rat liver.

Vinyl chloride monomer used in the manufacture of polyvinyl chloride is a chemical of increasing industrial importance but has recently been incriminated as a carcinogen, producing a mutagenic effect after being metabolized to active metabolites. The initial effect of vinyl chloride monomer and two of its presumed metabolites, chloracetaldehyde and chloroethylene oxide, on DNA synthesis was investigated in vivo in regenerating rat liver. The established control curve for the DNA synthesis rate after partial hepatectomy demonstrated two waves of synthetic activity at 21 and 30 h. Vinyl chloride, injected intravenously immediately on completion of the operation, depressed the first wave of DNA synthesis by 49.6%. The second peak of DNA synthetic activity was similar to that of the control. Chloracetaldehyde and chloroethylene oxide both produced similar effects on the first wave of DNA synthesis after partial hepatectomy, inhibiting the DNA synthesis rate by approx. 50%. After a regenerating period of 27 h, however, they produced very different effects, chloroethylene oxide raising the control DNA synthesis rate at 30 h by 49% while chloracetaldehyde tended to desynchronize the well-defined second peak of the control. The test compounds have been compared to literature reports of the inhibitory effects of various carcinogens on DNA synthesis.


Influence of mannitol on maintaining coronary flows and salvaging myocardium during ventriculotomy and during prolonged coronary artery ligation.

We investigated whether prolonged infusion of hypertonic mannitol results in a sustained increase in coronary flow and reduces myocardial necrosis after ventriculotomy or two hours of circumflex coronary artery occlusion. Cardiac outputs, intracardiac pressures, and heart rates did not differ between mannitol and control animals. Those receiving mannitol after ventriculotomy had coronary flows to myocardium near the incision which did not differ from controls. During coronary occlusion, mannitol did increase flow to ischemic and peri-ischemic regions by one hour, but this increase was not sustained at two hours. On histologic examination, myocardial necrosis involving the right ventricular free wall in the ventriculotomy animals and the posterior papillary muscle and subadjacent free wall in the coronary occlusion animals, did not differ between the mannitol treated and control groups. The data obtained in the present study, combined with those from earlier evaluations of the influence of mannitol during ventriculotomy and myocardial ischemia, suggest that mannitol's ability to increase coronary flow to injured areas of myocardium is relatively short-lived.


Efficacy of ambulatory systemic vasodilator therapy with oral prazosin in chronic refractory heart failure. Concomitant relief of pulmonary congestion and elevation of pump output demonstrated by improvements in symptomatology, exercise tolerance, hemodynamics and echocardiography.

The long-term efficacy of the new oral vasodilator, prazosin (PZ), was evaluated in nine patients with refractory heart failure due to chronic coronary heart disease. Ventricular function was assessed by cardiac catheterization, echocardiography, and treadmill testing; symptomatic evaluation was carried out for two to four months. One hour following 2-7 mg PZ, control left ventricular filling pressure was reduced (32 to 18 mm Hg, P less than 0.001) and cardiac index was elevated (1.95 to 2.89 L/min/m2, P less than 0.001) for a 6-hour period. After two weeks of PZ 2 to 7 mg four times daily, echographic end-diastolic dimension fell (5.7 to 5.4 cm, P less than 0.001) while shortening fraction increased (27.6 to 30.2%, P less than 0.005). Treadmill exercise duration increased from 209 to 317 seconds (P less than 0.001). Symptoms diminished throughout the duration of follow-up (mean 94 days) with improvement in NYHA functional class (3.7 to 2.2, P less than 0.001). Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous systems and is effective in the ambulatory management of chronic severe heart failure.


Effects of digitalis on resting and isometric exercise myocardial perfusion in patients with coronary artery disease and left ventricular dysfunction.

Digitalis has been shown to improve the impaired ventricular function associated with coronary artery disease as well as to increase myocardial oxygen consumption and produce coronary vasoconstriction. To elucidate the net result of these contrasting effects, six patients with coronary artery disease and left ventricular ejection fractions less than 0.50 had 1.0 mCi thallium-201 injected intravenously at rest and during three minutes of 33% of maximal handgrip, off and on 0.25 mg daily maintenance digoxin. Thallium-201 scintigram images were taken 30 minutes later and were computer processed with orthogonal linearly interpolated background subtraction and maximal count density equalization. Processed images were visually graded on a 0, 1, or 2 scale for 18 sectors--nine from the AP projections and nine from the 40 degrees left anterior oblique projections. A score resulting from the summation of the 18 sector grades was made for each study, the maximum score being 36. Off digitalis, patients performing handgrip exercise decreased their scintigram scores from 25.7 +/- 1.5 (mean +/- SEM) to 23.0 +/- 1.0, P less than 0.05. When patients were on maintenance digoxin, scores did not change significantly during handgrip exercise. Post exercise scores were significantly higher on digoxin than off (P less than 0.05), whereas, resting scores were unaffected by digoxin. These data suggest that myocardial perfusion, as measured by thallium-201 uptake, is improved in patients on digitalis who have coronary artery disease and left ventricular dysfunction.


Serum glycoproteins in coronary artery disease.

Serum glycoprotein levels were compared in two groups of age- and sex-matched patients, 15 with coronary artery disease and 14 normal controls. While total glycoprotein levels were increased in the coronary group, significantly higher levels were found in only five of 16 glycoproteins--C3c haptoglobin, GC-globulin, alpha1-acid glycoprotein, and C3 activator--with no change in 10 other glycoproteins and significant decrease in transferrin. This study demonstrates what appears to be a glycoprotein profile in coronary artery disease and reviews possible interactions of glycoproteins with known risk factors in atherogenesis.


The Erysichthon syndrome. Progression of coronary atherosclerosis and dietary hyperlipidemia.

One hundred nineteen patients with coronary artery disease confirmed by coronary arteriograms were studied. Cine coronary arteriography confirmed progression of atherosclerosis in 106 (89%) patients (mean age 50.9 yr) and nonprogression in 13 (11%) patients (mean age 50.3 yr). Progression was defined as follows: any increase to 50% stenosis, 50% to 75% narrowing, 75% to 90%, 90% to 99%, 99% to total occlusion. Only one patient of the 106 who progressed (less than 1%) had ideal values for both cholesterol and triglyceride. Three of 13 patients (23%) who did not progress had ideal lipid values (P less than 0.005). Fifty four of 106 patients who progressed had cholesterol levels greater than or equal to 250 mg%; none of 13 patients who did not progress had such levels (P less than 0.005). Thirty-nine of 98 (40%) patients who progressed had hypertension; only one (8%) who did not progress had hypertension (P less than 0.025). Seventy-four of 96 patients who progressed were smokers (77%); two of 13 nonprogression patients smoked (15%) (P less than 0.005).


A study of left ventricular function in coronary patients before and after physical training.

Fifteen subjects recovering from a myocardial infarction or suffering from angina were given a maximum effort test on a bicycle ergometer and hemodynamic and angiographic investigations before and after a period of physical training. The training program consisted of three sessions of 60 to 75 min each week for two months. Maximum effort tests showed that physical capacity had increased by 17% (P less than 0.02) and that for the same amount of effort the heart rate had decreased by 13% and the blood pressure by 7% (P less than 0.01). Hemodynamic and angiographic investigations showed no significant changes after training in the left ventricular end-diastolic pressure, ventricular volume, ejection fraction, VCF, percentage of shortening and segmental contractility, in the total group, in those patients whose contractility was considerably impaired, or in those who had large dyskinetic areas or widespread akinesia. It is concluded that training had no direct influence on the myocardium, either beneficial or detrimental.


Immediate effect of contrast medium injection on left ventricular volumes and ejection fraction. A study using metallic epicardial markers.

The immediate effect of contrast medium injection on left ventricular (LV) volume, stroke volume (SV) and ejection fraction (EF) was evaluated from postoperative LV biplane cineangiograms of 10 patients with 4-6 epicardial markers placed at the time of coronary artery surgery. After calibrating marker distances with respect to volume (r = 0.97-0.99) over one cardiac cycle for each patient, regression equations were used to compute LV volume from marker measurements for beats prior to, during and following injection. End-diastolic volumes (EDV) prior to injection ranged from 93-263 ml and did not change significantly with injection. End-systolic volumes (ESV) showed a mean decrease of 7.3 ml by beat 7 following injection; this was of borderline significance. Similarly, there was no significant change of SV or EF until beat 7 when there were small but significant increases of 6.4 ml and 0.04, respectively. The injection of moderate amounts of contrast in man does not cause significant changes in LV volume or EF through the sixth post-injection beat.


Termination of ventricular tachycardia by an increase in cardiac vagal drive.

Out of 12 patients in whom phenylephrine terminated ventricular tachycardia, four were selected for detailed studies of its mechanism of action. Pretreatment with edrophonium (15-20 mg, i.v.) decreased, while atropine (2.4 mg, i.v.) increased by at least a factor of two, the dose of phenylephrine required to break ventricular tachycardia. Carotid sinus massage following pretreatment with edrophonium in unusually high (15-20 mg, i.v.) doses broke ventricular tachycardia in all four patients. The evidence presented supports the assumption that a vagal mechanism caused both instances of termination. These findings significantly alter our interpretation of vagal interventions in the bedside clinical diagnosis of wide QRS complex tachycardias.


Echocardiographic and hemodynamic relationships of ejection sounds.

The physiologic correlates of ejection sounds have been studied by simultaneous phonocardiograms, echocardiograms and high fidelity pressure tracings. Ejection sounds associated with semilunar valve stenosis or hypertension of the systemic or pulmonary circulation occur at the moment of complete opening of the aortic or pulmonary valve recorded echocardiographically. The start of opening of these valves occurs at the onset of the pressure rise in the corresponding great vessel and completion of valve opening always occurs on the pressure upstroke. The ejection sound in the presence of stenotic valves occurs with checking of the opening motion of the thickened valve cusps. Although the hypertensive ejection sounds also occur at the precise moment of full opening of the valve it remains to be seen whether this relationship is causal or coincidental.


Limitations of the echocardiogram in diagnosing valvular vegetations in patients with mitral valve prolapse.

In order to assess the reliability of the echocardiogram in detecting valvular vegetations in patients with mitral valve prolapse (MVP), echocardiograms from 85 consecutive patients with mitral valve prolapse were reviewed. Eleven patients had thick shaggy echoes confined to the anterior mitral leaflet; eighteen patients had shaggy echoes on the posterior leaflet; and five had abnormal echoes on both the anterior and posterior leaflets. Only one patient had clinical evidence of infective endocarditis. Redundant leaflets which present multiple surfaces for the production of echoes may explain the abnormal echoes that were observed. Patients with echographic features suggesting mild prolapse less commonly exhibited shaggy leaflet echoes than those with more severe prolapse. Because a significant proportion (40%) of patients with MVP had shaggy echoes which closely resembled those seen in valvular vegetations, we feel that the echocardiogram is of limited value in diagnosing infective endocarditis in patients with mitral valve prolapse.


Echocardiography of right ventricular tumors.

The clinical and echocardiographic findings of four patients with right ventricular tumors (three myxomas and one metastatic melanoma) are presented. All four patients previously had been evaluated by competent cardiologists, and the diagnosis of a right ventricular tumor was missed. The initial echocardiograms were interpreted as not showing any right ventricular tumor; but on review we found that the correct diagnosis could have been made. The presence of the right ventricular myxomas was confirmed at angiography and surgery. However, the attachment of the stalk of the mycoma could not be determined confidently by angiography alone, and in two of the three cases two-dimensional echocardiography was required to identify correctly the location of the base of the stalk. This paper emphasizes the usefulness and technical difficulties of M-mode and two-dimensional echocardiography in the diagnosis of a right ventricular tumor.


Two-dimensional echocardiographic findings in atrial septal defect.

Two-dimensional echocardiographic findings in a group of 24 patients with atrial septal defects were correlated with findings obtained by cardiac catheterization and M-mode echocardiography. The prevalence of mitral prolapse was 95% by two-dimensional echocardiography and 59% by angiography in patients with secundum and sinus venosus atrial septal defects. The majority of the group with echocardiographic prolapse manifested a distinctive pattern of prolapse, with predominant involvement of the anterior mitral leaflet. Thirty-eight percent of the patients in this series manifested paradoxical septal motion by M-mode and/or two-dimensional echocardiography. In the patients with abnormal septal motion, the net systolic anterior movement of the septum was caused by an exaggerated systolic anterior movement of the main body of the left ventricle. The atrial septal defect could be visualized with confidence by two-dimensional echocardiography only in the two patients with ostium primum atrial septal defects. Cleft anterior mitral leaflets were also clearly demonstrated in these two patients.


Evaluation of left ventricular size and function by echocardiography. Results in normal children.

Left ventricular (LV) size and function were studied by echocardiography in 145 normal children. The LV end-diastolic diameter (EDD) and its percentage change with systole (%deltaLVD) were measured and mean velocity of circumferential fiber shortening (Vcf) calculated. The LV pre-ejection period (PEP) and ejection time (LVET) were determined from recordings of aortic valve motion. The EDD increased by approximately threefold during childhood and was best correlated with the log of body weight (r = 0.95) and the log of body surface area (r = 0.96). The mean %deltaLVD was 36 +/- 4 (SD), and this index of LV function was independent of age and heart rate. Mean Vef was higher, and the absolute values of PEP and LVET shorter, in younger children with a faster heart rate. The mean ratio of PEP/LVET was 0.31 +/- 0.003, and was relatively independent of age (r = 0.41) and heart rate (r = 0.37). The %deltaLVD and PEP/LVET appear to be particularly useful indices of LV function because they remain constant during the course of childhood.


The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure.

Twenty-five patients with left ventricular failure and low cardiac output received a 72 hour infusion of dobutamine (10-15 microgram/kg/min) in order to determine the cardiovascular properties of this new inotropic agent. Left ventricular contractile performance improved significantly during the infusion as measured by systolic time intervals and echocardiographic parameters. Mean PEP/LVET decreased from 0.76 +/- 0.03 to 0.58 +/- 0.03 (P less than 0.05). The percent change in internal dimension of the left ventricle from diastole to systole increased from 9.5 +/- 1 to 16.8 +/- 1 (P less than 0.05) and Vcf increased from 0.47 +/- 0.05 to 0.80 +/- 0.06 circ/sec (P less than 0.05). Mean cardiac output (nine patients) rose from 1.97 +/- 0.15 to 3.33 +/- 0.50 L/min/m2 while mean pulmonary capillary wedge pressure fell from 28 +/- 3 to 18 +/- 2 mm Hg during the infusion period (both P less than 0.05). These changes in cardiac function occurred without significant changes in heart rate, ventricular irritability, or blood pressure. Urine flow and urine sodium concentration increased during the infusion period. The improvement of cardiac function without the simultaneous development or exacerbation of undesirable effects (tachycardia, premature ventricular contractions, increased pulmonary or systemic resistance, tachyphylaxis, etc.) makes dobutamine a highly desirable inotropic agent.


Systemic collateral and pulmonary artery stenosis in patients with congenital pulmonary valve atresia and ventricular septal defect.

Angiograms of 30 patients with congenital pulmonary valve atresia, ventricular septal defect, and large systemic-pulmonary collateral arteries (SPCAs) were evaluated. All had aortography, 28 had SPCA arteriography, and 26 had right ventriculography. Seventeen (65%) of 26 patients had a right ventricular infundibulum, 23 (77%) had a pulmonary artery confluence, and five of the nine patients without a right ventricular infundibulum had a confluence. Sixty-six SPCAs of aortic origin were seen; 28 (42%) had narrowing and 21 patients (70%) had one or more narrowed SPCAs. Five patients had collaterals from internal mammary, subclavian or innominate arteries. Fourteen (47%) had hilar pulmonary artery stenosis. Of these 14 patients mild peripheral stenosis was demonstrated in five. Right aortic arch was present in 15 patients (50%). Complete angiographic delineation of pulmonary vasculature is an essential procedure for preoperative detection of pulmonary and SPCA stenoses in these patients.


The status of cardiovascular health knowledge among sixth, seventh, and eighth grade children.

The goals of this study were to develop and standardize a test of cardiovascular health knowledge to determine its status among primary school children, to ascertain the rate at which cardiovascular health knowledge increases as compared to other subject areas, and to demonstrate the feasibility of the use of standardized achievement tests for assessing the results of health education curricula. The Iowa Cardiovascular Health Knowledge Test (ICVHT) was developed and administered in conjunction with a standardized educational testing program, the Iowa Test of Basic Skills (ITBS), to a stratified sample of 2,675 Iowa Students from grades six, seven, and eight. The average student in the sixth, seventh and eighth grades answered 37.9 +/- 0.4, 41.2 +/- 0.3, and 43.7 +/- 0.4 (SEM) percent of the items correctly. ICVHT scores increased minimally (less than 1 item/grade) as  grade levels increased, but at a 75% slower rate than scores in other subjects tested. The results document a deficiency in cardiovascular health knowledge and provide a model for use in educational assessment programs in other health disciplines.


Conjoined thoracopagus twins.

A case of vaginally delivered stillborn female thoracopagus conjoined twins is presented. Each twin had a cleft lip and cleft palate. They shared a common pericardial sac and a common abdominal cavity. The liver was conjoined, and the small bowel was common to both twins. One twin was asplenic. Although the twins were monozygotic, their viscera were neither identical nor mirror-image to each other, and the visceral anomalies were unique to each twin. The hearts were fused, and communications existed between the circulations at the atrial and ventricular levels. One twin had single atrium, solitary (right) ventricle, malposed great arteries, pulmonary valvular atresia and infundibular stenosis, right aortic arch with aberrant left subclavian artery and with left ductus arteriosus, and atresia of the common pulmonary vein. The other twin had two atrial septal defects of the fossa ovalis and sinus venosus types, partial anomalous pulmonary venous connection, persistent left superior vena cava to coronary sinus, solitary (left) ventricle, malposed great arteries, and left aortic arch with aberrant right subclavian artery and with left ductus arteriosus. There was atrial and ventricular fusion. On hypothetical grounds, and in a comparable anatomic situation, salvage of one twin might be possible by surgical means, while the other twin was sacrificed.


Early saphenous vein grafting after subendocardial infarction. Immediate surgical results and late prognosis.

In a prospective study of subendocardial myocardial infarction (SEI), 64 patients underwent coronary arteriography and left ventriculography early after their SEI. Of these 64 patients, 28 had saphenous vein grafting (SVG) performed within 3 months of SEI. The majority of this surgical group (24 of 28 patients) were operated on because of unstable angina following their SEI. Of these 28 patients, three suffered a perioperative myocardial infarction (10.7% incidence) and another patient died immediately postoperative (3.6% mortality). At a mean follow-up period of 16 months, 22 of these 28 patients (78%) were free of angina; in addition, there were no late deaths or recurrent myocardial infarctions in this surgical group. Therefore, SVG appears to improve the functional status of the majority of this group of patients with a complication rate at surgery comparable to that reported for unstable angina alone.


Mitral valve replacement in medically unresponsive congestive heart failure due to papillary muscle dysfunction.

Forty patients with a mean age of 65 years (range 44-76 years) were operated on; 30 of 40 patients (75%) had prior myocardial infarction. All had severe therapy-resistant congestive heart failure, 75% (30 of 40 patients) were symptomatic at rest, and 25% (10 of 40 patients) were symptomatic on minimal exertion. Cardiac index ranged from 1.24-2.84 L/min/m2 (mean 1.99). Left ventricular end-diastolic pressure ranged from 3-36 mm Hg (mean 18). All patients had significant mitral insufficiency and contractility was reduced markedly to moderately in 63% (25 of 40 patients). Significant coronary artery disease (obstruction greater than or equal to 75%) was present in all patients. All had mitral valve replacement, 30 had bypass surgery, and 7 left ventricular aneurysmectomy. Five died during surgery or before discharge (early mortality 12.5%). After a mean follow-up period of 16 months, another eight patients died, two with causes not related to the cardiovascular system (total mortality 32.5%). Of 20 patients with a cardiac index greater than or equal to 1.5 L/min/m2 and an ejection fraction greater than or equal to 0.40, 17 survived surgery and improved postoperatively. Mitral valve replacement for this group of patients is recommended.


Valve replacement in children.

Since 1964, 27 valve replacements have been performed in patients who ranged from 5 months to 20 years of age. Fourteen underwent aortic valve replacement, 10 underwent mitral valve replacement, two had systemic atrio-ventricular valve replacement, and one had tricuspid valve replacement. Nineteen patients had congenital heart disease, five had rheumatic disease, and three had Marfan's syndrome. Starr-Edwards prostheses were used in 17 patients, Björk-Shiley prostheses in six, and procine xenografts in for. There were five early deaths and five late deaths. Patients were followed for 2 months to 6 years postoperatively (mean 2.1 years). All survivors showed clinical improvement. There were no episodes of thromboembolism. Minor bleeding, arrhythmias, and bacterial endocarditis occurred infrequently.


Angiographic predictors of survival following left ventricular aneurysmectomy.

Sixty-four consecutive patients with coronary artery disease who had resections of left ventricular scars during 1969 to 1973 were retrospectively identified. Extent of angiographic coronary artery disease was scored by the jeopardy score system. Size of the abnormally contracting segment (akinetic or dyskinetic in all) was measured as a percent of the end-diastolic ventriculographic perimeter (% ACS). Contractility of the non-ACS was expressed as the difference between the actual ejection fraction and that predicted by the spherical model of Feild and Dowling (excess ejection fraction, XEF.) Perioperative survival correlated with jeopardy score (21 of 27, jeopardy score less than or equal to 6; 19 of 37 jeopardy score greater than 6) and with XEF (30 OF 38, XEF greater than +0.10; 10 of 26, XEF less than or equal to "0.10). When XEF and jeopardy score were combined, the patients were separated into four subgroups with perioperative survival ranging from 89% to 33%. Long-term survival (minimum follow-up period 30 months) in the 40 perioperative survivors also correlated with jeopardy score (95% at 54 mo for jeopardy score less than or equal to 6; 49% for jeopardy score greater than 6). Survival was unrelated to whether or not aortocoronary bypass graft procedures had been done. It is concluded that survival following aneurysmectomy is predicted by two preoperative angiographic variables--the extent of coronary artery disease and the contractility of the non-aneurysmal portion of the left ventricle.


Clinical and hemodynamic results following triple valve replacement: mechanical vs porcine xenograft prostheses.

This study summarizes the results in 26 patients of triple valve replacement (TVR) performed between 1967-1975. The first ten patients (group I) received all-mechanical valves, but the last 16 (group II) received porcine xenograft atrioventricular and porcine or mechanical aortic valves. Preoperatively, all patients were functional class II or IV with pulmonary arterial and venous hypertension. Early mortality was 30% group I and 18.8% group II; late mortality has been 30% group I and 6.3% group II. Total operative and bypass time, and duration of postoperative respiratory support was less (P less than 0.025) in group II than in group I. Postoperative catheterization performed in 16 of 26 patients demonstrated significant reduction (P less than 0.05) in pulmonary arterial and venous hypertension, and aortic and mitral gradients in group II. There have been no late complications or valve malfunctions in group II. An improvement of at least two functional classes was seen in 4/6 group I and 12/13 group II operative survivors. The results of TVR with porcine xenografts compare favorably with those of all-mechanical replacements and deserve further evaluation.


Aortic valve replacement: a ten-year follow-up of non-cloth-covered vs cloth-covered caged-ball prostheses.

From 1965 to 1976, 721 isolated aortic valve replacements were performed at the University of Oregon hospitals, utilizing Starr-Edwards caged-ball prostheses. Three models of aortic prostheses were introduced during this period: a non-cloth-covered model has been in continuous use since 1965; a cloth-covered model was begun in 1968 and has been supplanted by the modified composite-strut or "track" model since 1972. The 5-year actuarial survival rate for operative survivors is about 80% for both non-cloth-covered and cloth-covered valves, while the 10-year survival is 61%, based on the older model only. The actuarially-determined percentages of patients experiencing significant thromboembolic episodes (i.e., all except transient ischemic episodes) at 5 years are 7% for the cloth-covered and 9% for the non-cloth-covered model. If transient ischemic attacks are included, the cloth-covered model has only an 8% incidence at 5 years compared to a 22% incidence for the older model. However, the cloth-covered valves are subject to a higher risk of reoperation because of the possibility of cloth injury. The "track" valve, therefore, was designed with exposed metal on the inner surface of each strut to prevent ball-cloth contact. In 107 patients (mean follow-up period 1 year) receiving anticoagulation, this prosthesis has maintained the same low incidence of thromboembolism as the previous cloth-covered model, with no reoperations for valve failure.


Quantification of wear, hemolysis and coagulation deficits in patients with Beall mitral valves.

Fifty-five patients (35 females and 20 males) were studied by noninvasive means 3.5-8.6 years after isolated mitral valve replacement with Models 103 and 104 Beall prostheses. History and physical exams by three physicians, complete hemograms, SMA 18, iron excretion rates, and coagulation profiles were performed. Additionally, electrocardiograms, echocardiograms, phonocardiograms, cardiac series, and high-speed cinefluorography of the prostheses were obtained. Valve wear was assessed by the disc/cage ratio measured from a "three-legged view" with magnification. At a mean duration of 5.85 years after operation, the entire group had a mean disc/cage ratio of operation, the entire group had a mean disc/cage ratio of 0.906 +/- 0.031 vs a normal value of 0.944 +/- 0.014. The group was mildly anemic and had a urinary iron loss that was 40 times normal. The lactic dehydrogenase (LDH) concentration was more than five times normal. The coagulation profiles were abnormal with respect to the bleeding and stypven times, antiheparin activity, fibrin degradation products, and megathrombocyte index. These abnormalities were unrelated to sex, degree of valve wear, and history of thromboembolism. Males were less anemic and had higher urine iron losses than females. Nine patients with severe valve wear (disc/cage ratio less than or equal to 0.87) were significantly more anemic with large urine iron losses and had elevated total bilirubin, serum glutamic oxaloacetic transaminase, and LDH concentrations (ninefold), when compared to nine patients with minimal wear (disc/cage ratio greater than or equal to 0.925). It is emphasized that the findings of a significant anemia, an LDH concentration greater than 1500 mU/ml, and a disc/cage ratio of less than 0.87 in a patient with an isolated Beall mitral valve prosthesis are indicators for the need to replace the prosthesis in the near future. Re-replacement is urged before significant clinical deterioration.


Effects of membrane stabilization on the safety of hypothermic arrest after aortic cross-clamping.

Twenty dogs underwent 1 hour of topical hypothermic arrest; five were untreated, five received methyl prednisolone (30 mg/kg), five received 0.2% procaine, and five received both drugs. Arrest was almost immediate (less than 2 min) with procaine, but was delayed 14 +/- 3 minutes in the other groups. Steroid-treated dogs had the highest post-ischemic left ventricular (LV) blood flows (110 +/- 22 cc/100 g/min) (P less than 0.05). Membrane-stabilizing drugs did not prevent myocardial edema; LV water rose 2% (P less than 0.01) in all groups. Post-ischemic LV compliance was depressed most (55%) in the untreated group, and less after procaine (30%) (P less than 0.05). Postischemic LV performance was depressed 44% (P less than 0.01) in the untreated dogs, and returned to near normal levels with steroid (89% recovery), procaine (97% recovery), and both drugs (95% recovery). We conclude that steroids and/or procaine protect against postischemic myocardial depression but do not prevent myocardial edema. Combining steroids and procaine provide no apparent added benefit, but procaine has the technical advantage of almost immediate cardioplegia.


Optimal conditions for reperfusion during cardiopulmonary bypass.

An experiment was designed to determine optimal methods of myocardial reperfusion after normothermic ischemic arrest in the in vivo pig heart. Four variables were studied: 1) ischemic arrest for 15 minutes repeated six times vs 30 minutes repeated three times: 2) coronary reperfusion between each arrest period lasting 5 or greater than or equal to 15 minutes (the latter duration dependent upon electrocardiographic reversal of ischemic); 3) perfusion pressure of 50, 75, or 100 mm Hg; and 4) a beating or fibrillating heart during reperfusion. The effects of perfusion were monitored by measuring the endocardial/epicardial perfusion ratio (with ratioactive microspheres), coronary blood flow, and coronary reactive hyperemia by measuring coronary vascular resistance during reperfusion. Electron micrographs were examined to determine if subtle distinctions between groups could be measured. A total of 78 pigs (60 experimental and 18 control) were evaluated. The experimental animals were divided into 10 groups of six pigs each. In each group only one of the four variables (beating or fibrillating ventricle, perfusion pressure, duration of ischemia, and duration of reperfusion) was altered to provide comparative data. Results are based on improved endocardial perfusion and a greater coronary reactive hyperemic response when comparing each experimental group to one another and to control animals. Reperfusion of a contracting rather than fibrillating ventricle resulted in improved endocardial flow as did reperfusion at a low (50 or 75 mm Hg) rather than a high (100 mm Hg) perfusion pressure. A short ischemic interval repeated six times rather than a longer ischemic interval repeated three times also allowed for improved subendocardial perfusion and a greater reactive hypermic response as did a longer reperfusion period between equal ischemic intervals. Electron microscopic studies showed a gradation of abnormalities ranging from little deviation from control in beating hearts and short ischemia and long duration, low pressure reperfusion to marked mitochondrial vacuolization in fibrillating hearts subjected to long ischemia, short reperfusion at high perfusion pressures. The best technique for myocardial reperfusion based on available data is to provide reperfusion of adequate duration in order to reverse the ischemic electrocardiogram in a beating heart, avoiding an excessively high perfusion pressure.


Autopsy study of unoperated abdominal aortic aneurysms. The case for early resection.

A review of 24,000 consecutive autopsies during a 23-year period from 1952 through 1975 at the Massachusetts General Hospital revealed 473 patients died with surgically intact arteriosclerotic abdominal aortic aneurysms (AAA). Contrary to previous studies, the incidence of rupture of AAA between 4 and 7 cm in our experience is similar and significant (25%). The location of rupture and duration of symptoms were recorded. Of the multiple-risk factors considered, only size seemed to bear on the likelihood of AAA rupture. Of 52 patients followed 3 months to 10 years before death with known AAA, the majority died of the ruptured AAA. In a surgical environment with an expected mortality of less than 2%, even small aortic aneurysms should be resected.


Assessment of abdominal aortic aneurysm size.

Because of the importance of size in the decision for elective operation in patients with abdominal aortic aneurysm (AAA) and the need to identify accurately even small aneurysms, a prospective study was carried out to compare currently available diagnostic methods. A series of 78 patients with AAA underwent evaluation by physical examination, lateral lumbar spine X-ray, aortic ultrasound, and aortography. Measurements were compared to aneurysm size at operation. Physical examination was most variable, and tended to overestimate size by approximately 20%. Lateral spine X-ray was useful in three of every four patients and in these cases it was reliable and reasonably accurate. Ultrasonography was most widely applicable and very reliable for diagnosis. Its tendency to underestimate aneurysm size in our experience may be improved by use of gray-scale units, which better define aneurysm wall thickness. The anatomic information provided by aortography was of great value in the surgical management of patients with AAA, but aortography was of limited value in accurate measurement and should not be employed for this purpose.


Combined aneurysmal and occlusive arterial disease.

Acute arterial occlusion secondary to embolization from aneurysms located upstream occurred in 16% in 277 aneurysms involving subclavian, abdominal aortic, femoral, and popliteal vessels. This association should be suspected in those instances when the occlusive symptoms are severe and sudden in onset. The study emphasizes the importance of aortic outlining, as well as arteriographic mapping of both lower extremities, when occlusive disease of one or both legs is present. An aneurysm upstream should be suspected when there is failure of a previously implanted graft peripherally. Asymptomatic, small abdominal aortic aneurysms should be resected.


Large vessel impedance in peripheral atherosclerosis.

Recent studies based on an animal model of arterial stenosis have shown that large vessel impedance (ZL), determined from the high-frequency vascular hydraulic impedance of a stenotic femoral arterial bed, is linearly related to the large vessel stenotic resistance, and somewhat independent of distal (small vessel) arteriolar resistance. To determine the applicability of these findings on human subjects with stenotic atherosclerotic lesions, ZL was determined in the femoral arteries of 17 patients (at the time of reconstructive operations) with no (N), mild (AS), and severe (occlusive) atherosclerotic (ASO) disease, and in a group of patients before and after femoral-to-popliteal bypass procedures (FEM-POP). Data were collected under steady-state conditions (SS) and during peak flow after a 30 mg bolus intra-arterial administration of papaverine hydrochloride (PAPAV). The ZL was found to be significantly greater (P less than 0.05) for the ASO group than for the N group at SS and after PAPAV administration. There was no significant difference in ZL between the SS and PAPAV conditions for all groups. The ZL decreased significantly (P less than 0.01) from the pre- to post-bypass conditions (with and without the stenosis), at steady-state and after papaverine hydrochloride administration. Large vessel impedance appears to provide a reliable index of the severity of a large vessel atherosclerotic stenosis, and is indpendent of small vessel resistance in humans. These findings are consistent with those of previous experimental animal studies.


Regional ischemia distal to a critical coronary stenosis during prolonged fibrillation--improvement with pulsatile perfusion.

In a previous study from this laboratory, regional myocardial ischemia developed distal to a critical coronary stenosis in the fibrillating heart on cardiopulmonary bypass when myocardial perfusion was non-pulsatile. To assess the effect of pulsatile perfusion on the development of the fibrillation-induced ischemia, 10 dogs were placed on total cardiopulmonary bypass with the heart in the vented fibrillating state. A critical stenosis was applied to the left anterior descending artery (LAD). Pulsatile perfusion with a pulse pressure of 35 mm Hg and a pulse rate of 100/min was produced by a new method developed in this laboratory. During the 2 hours of bypass, ischemia in the LAD-supplied myocardium was assessed by changes in intramyocardial oxygen (PmO2) and carbon dioxide (PmCO2) tensions and by regional arterial-coronary venous lactate difference. With linear perfusion, regional ischemia in the LAD myocardium had been evidenced by a low PmO2 (8 +/- 3 mm Hg), a high PmCO2 (170 +/- 25 mm Hg) and regional lactate production (9.2 +/- 4.2 mg/100 ml). In contrast with pulsatile perfusion intramyocardial gas tensions remained stable during the 2 hours on bypass (PmO2 = 21 +/- 3 mm Hg, PmCO2 = 65 +/- 5 mm Hg, P less than 0.05 vs linear flow study) and lactate consumption was demonstrated (+17.7 +/- 2.9 mg/100 ml, P less than 0.001 vs linear flow group). With linear perfusion, myocardial blood flow to the LAD area had decreased 56 +/- 8% in the subendocardial layer and 46 +/- 7% in the subepicardial layer. In the dogs receiving pulsatile flow during bypass, regional LAD blood flow remained unchanged over the 2-hour bypass period and was significantly higher than the flow with linear flow (P less than 0.05). These data indicate that fibrillation-induced regional myocardial ischemia distal to a critical stenosis can be prevented by maintaining pulsatile perfusion during cardiopulmonary bypass.


Reduction of unexpected, life-threatening events in postoperative cardiac surgical patients; the role of computerized surveillance.

With increasing use of computerized surveillance (CS) in critical care, a key question is whether it favorably influences clinical outcome. Knowing that two intensive care unit beds would soon have CS capability, we embarked on an uninterrupted prospective study in which the incidence of sudden, unexpected life-threatening events (SULTE) was compared in post-open heart surgery patients whose subsystem performances were evaluated by conventional methods (CM) as opposed to those who would be followed by CS involving automatic acquisition and generation of 30 cardio-respiratory variables. We evaluated 211 patients, 91 with CM and 120 by CS. Since CS availability was limited, sicker patients were given priority for the two CS beds. Despite the obvious bias in favor of CM, there was a statistically significant reduction (P less than 0.001) in the incidence of SULTE in those patients followed by CS (1 of 120 patients: 0.8%; no SULTE-related deaths) in comparison to the CM patients (11 of 91 patients: 12%; two SULTE-related deaths.) The data suggest that computerized surveillance can play a role in reducing morbidity and possibly mortality in postoperative cardiac surgical patients.


Myocardial injury following myocardial revascularization. Detection by isoenzyme analysis.

To clarify the value of isoenzymes in the detection of acute myocardial injury (AMI) associated with coronary artery bypass grafting, 350 consecutive patients (804 grafts) were evaluated with serial electrocardiograms (ECG) and serum levels of serum glutamic oxaloacetic transaminase (SGOT), total creatinine phosphokinase (CPK), and lactic dehydrogenase (LDH) on Days 0, 1,2,3,4,5, and 7. Graft patency 1 to 6 months postoperatively was 92%. Sixty patients (18%) had ECG evidence of AMI. Four patients died (1.1%) Of the 185 patients with serial LDH isoenzyme analysis, 46 had elevated cardiac fraction (LDH-1). Only 35 of these had AMI by ECG. The others had nonspecific ECG changes, but associated enzymatic andhemodynamic evidence of AMI. The CPK-MB band was elevated in all patients in the immediate postoperative period, but did not correlate with ECG, hemodynamic, or enzymatic evidence of AMI. The diagnosis of AMI following coronary artery bypass could not be substantiated by evaluation of total LDH, CPK, or CPK-MB. LDH-1 is specific in detecting AMI after a coronary artery bypass graft.


Left ventricular apical-abdominal aortic conduits for left ventricular outflow tract obstructions. Clinical results in eleven patients with a special composite prosthesis.

Cardiologists and surgeons are occasionally faced with therapeutic dilemmas regarding the management of recurrent left ventricular outflow tract obstructions, such as supravalvular, valvular, subvalvular or "tunnel" stenoses and obstructive myopathies. Following an extended series of biomaterial, hemodynamic, reliability and configuration studies in calves, we have created double-outlet left ventricles in 11 patients. All gradients were markedly reduced. All patients were discharged without anticoagulants, and the longest follow-up period is in excess of 1 year. In eight cases, the percent of cardiac output flowing antegrade and retrograde was quantitated with velocity-tipped catheters. An average ratio of 2:1 (antegrade [ascending aorta]: retrograde [composite conduit]) was found. The procedure is simple and effective in relieving primary or recurrent left ventricular outflow tract obstructions.


Long-term function of aortic homografts as the right ventricular outflow tract.

Physical examination, chest roentgenography, phonocardiography, and right heart catheterization were used to evaluate the function of composite aortic homografts inserted as right ventricular outflow tracts in 13 patients 1.8 to 7 years previously. All homografts in these patients who were followed for 2 or more years demonstrated calcification of the aortic wall, but valve leaflets were spared. Moderate pulmonary insufficiency was present in eight patients with single cusp partial homografts, but was well tolerated in all. Homograft valve insufficiency was mild in five patients with complete homografts. No patient had an outflow tract gradient greater than 32 mm Hg. The average gradient was 18.5 +/- 2.7 (SEM) mm Hg. Abnormality of pulmonary blood flow was found in three patients and could be related to previous Waterston or Potts anastomoses. No late morbidity due to homograft degeneration has occurred and the long-term function of these conduits appears to be good.


Postoperative investigation of left ventricular aneurysm resection.

We reviewed 35 patients undergoing resection of a chronic postinfarction left ventricular aneurysm. There was 5.7% operative mortality. Of the long-term survivors, 80% are functional class I or II. Ten patients had postoperative left ventriculograms studied by means of a computerized analysis of endocardial motion using internal orthogonal and radial grids. Postoperative end-diastolic volumes were much greater than normal and large akinetic areas were present although there was good improvement in the patient's functional capacity. Grid analysis of endocardial motion correlated better with the patient's postoperative clinical status than did measurements of end-diastolic pressure and volume, ejection fraction, or visual inspection of the postoperative left ventriculogram.


Late results with synthetic valved external conduits from venous ventricle to pulmonary arteries.

Eighty-five patients operated on before January 1976 have survived at least 30 days after insertion of a valved external conduit by the venous ventricle (usually the right) and the pulmonary arteries as a part of the repair of their congenital heart disease. Follow-up information is available on 83 patients, and mean follow-up time has been 27.7 months. Seven patients have required reoperation because of obstructive complications. Actuarial analysis indicates that the proportion of patients requiring reoperation is 4.0 +/- 2.8% at 2 years, 12.9 +/- 5.5% at 3 1/2 years, and 30.4 +/- 12.1% at 5 years. In five patients compression of the conduit between the sternum and heart was the primary cause of the obstruction. The proportion requiring reoperation for conduit compression is 2.0 +/- 2.0% at 2 years, 8.6 +/- 4.9% at 3 1/2 years, and 27 +/- 12.4% at 5 years. Age at operation is not related to the proportion of patients requiring reoperation, nor is the type of conduit. No patients have yet required reoperation for conduit compression whose operation has been done since we began systematically to position the conduit well away from the sternum. By actuarial analysis the proportion of patients surviving 5 years is 76.7%. Of those alive at follow-up examination, 78% were without limitation of activity.


Ultrasound evaluation of abdominal aortic aneurysms.

Forty-eight patients undergoing elective repair of an abdominal aortic aneurysm were randomly selected for correlation of diagnosis of aneurysm and aneurysm size as determined by direct surgical measurements, ultrasound examination, and lumbar spine X-ray. The preoperative diagnosis was confirmed by lumbar spine plain films in 72% of patients and by B-mode ultrasound in all of patients. Aneurysm size could be measured by lumbar spine X-ray in 55% of patients and with gray-scale B-mode ultrasound in all of patients. The average difference between surgically measured and roentogenographically determined aneurysm size was 1.5 cm in the transverse diameter and 0.87 cm in the anteroposterior diameter of the aneurysm. The average difference between surgically measured aneurysm size and ultrasound-determined external wall diameter of the aneurysm was 0.42 cm in the transverse diameter and 0.29 cm in the anteroposterior diameter. From these data we conclude that gray-scale B-mode ultrasound of the aorta is a more sensitive and accurate method of assessing abdominal aortic aneurysms than is the use of lumbar spine X-ray.


Long-term results of the Mustard procedure.

Over a 10-year period, 123 patients with transposition of the great vessels underwent the Mustard procedure. The hospital mortality for the series was 10.6%. There were seven late deaths, five of which were presumable due to arrhythmia. Sinus rhythm was noted postoperatively in 53% of the patients. Almost all the survivors had achieved catch-up growth when evaluated 6 months to 10 years later. A growth spurt was more consistently seen in the patients who were operated on under 2 years of age. Physical endurance and school performance were on a par with their normal peers or better in about half of the survivors. Severe neurologic problems were present in five patients. Postoperative catheterizations in 42 patients showed a rather high incidence of residual interatrial shunts, mild left ventricular outflow obstruction, and mild superior vena caval obstruction. Pulmonary venous obstruction and serious tricuspid regurgitation were not encountered.


Mitral valve replacement: long-term evaluation of prosthesis-related mortality and morbidity.

Over a 12-year period isolated mitral valve replacement (MVR) was performed in 897 patients including 49 Starr-Edwards no. 6000, 519 SE no. 6120, 115 aortic allograft, and 214 porcine xenograft valves. Mortality and morbidity specifically related to the prosthesis was determined for each valve type. Fifty-two of 505 (10%) discharged patients with SE valves, four of 108 (3.7%) with homografts, no patients with heterografts, died of valve-related causes (P less than 0.05). Actuarial analysis shows continued time-related risk with any valve for both thromboemboli and valve failure. Thromboemboli were much more frequent with SE than with either tissue valve (P less than 0.05). Primary valvular incompetence was more common as a cause of valve failure with tissue valves (P less than 0.05), whereas multiple embolic episodes were more often a cause of valve failure with SE (P less than 0.05). Five of 49 (10%) patients with SE no. 6000, 30 of 519 (5.8%) with SE no. 6120, 19 of 115 (16.5%) with allografts, and two of 214 (0.9%) with xenografts needed reoperation for valve failure. For SE, homograft, and heterograft valves, actuarially determined composite, prosthesis-related mortality show 14% (80/568), 7% (8/115), 0% patients dead 6 years after MVR, respectively (P less than 0.05), while 3 years after MVR, 65% (369/568), 37% (42/115), and 85% (181/214) patients were free of prosthesis-related death or complications, respectively (P less than 0.05). Specific prosthesis-related complications differ between valve types significantly affecting survival and morbidity post-MVR.


Comparison of competitive protein binding analysis and radioimmunoassay for the determination of cortisol in serum and urine.

The determination of serum and urinary free cortisol by competitive protein binding and radioimmunoassay were compared on patient samples using two commercially available kits. In addition, the Beckman RIA kit reagents were examined for precision and accuracy through the performance of reproducibility, recovery, cross reactivity and parallelism studies on serum and urine. Analytical recovery experiments with cortisol added to urine and serum showed 90% and 97% recovery respectively with the RIA reagents. Good reproducibility and parallelism criteria were also obtained using Beckman kit reagents. Antiserum specificity was documented and demonstrated no cross reactivity with structurally related steroids at clinically normal serum concentrations.


Variables in the measurement of serum cholesterol by gas-liquid chromatography.

Gas-liquid chromatography (GLC) is an effective method for the measurement of total serum cholesterol. Its use in the clinical laboratory, however, requires careful attention to many variables (flow rate, sample size, sensitivity of solvent and choice of the quantitation method, i.e. peak-height ratio vs. peak height). This report evaluates the effect of these variables on the quantitation of serum cholesterol by GLC.


Copper interference in the determination of iron in serum using ferrozine.

Random samples of sera were analysed for copper and iron. Based on the data presented in this paper and substantiated by other workers, the ferrozine method for the determination of serum iron is the most sensitive method currently available, provided the interference due to copper is effectively eliminated.


Quantitative analysis of trace elements in human blood and plasma by energy dispersive X-ray fluorescence.

A photon excitation, secondary target x-ray fluorescence system was used to measure concentrations of Cu, Zn, Br and Rb in whole blood and plasma of healthy adults. The samples preparation method and calculated limits of detection of the technique are reported. Correlation statistics for elemental concentrations have been determined. Verification of the results for copper was performed using atomic absorption spectrophotometry.


The use of in vitro diagnostic kits in hospital laboratories in Canada.

1. A survey conducted among hospital laboratories has yielded data from 640 institutions concerning the use of diagnostic kits and reagents in Canada. 2. Kits designed to test for chemical constituents were most frequently used in hospitals of 51 to 600 bed capacity whereas the ones for enzymes were most extensively used in 201 to 700 bed-size institutions. Kits based on the CPB principles were generally used in hospitals of more than 200 beds whereas those based on RIA were only in frequent use where the bed capacity was 351 or more. 3. The following tests were most often performed by kits: aminotransferases, amylase, urea, LDH, phosphatases, glucose, CPK, bilirubin, calcium, uric acid, T-4, T-3, digoxin and vitamin B12. 4. The survey reflects a continuing and increasing usage of in vitro diagnostic kits and associated blood analyzer systems. It also indicates a significant adoption of assay kits which utilize RIA and CPB principles.


A random survey of drug screening proficiency.

There is little evidence of uniformity of standards of performance as influenced by technical capability and priority of concern for drug-screening proficiency. The objective of this quality-control survey was to illustrate the degree of error associated with toxicological analyses and encourage the use of controls to decrease the possibility of reporting erroneous findings.


Isoelectrofocusing of aldolase B from normal human livers and from livers with hereditary fructose intolerance.

By isoelectrofocusing in thin-layer acrylamide-ampholine gel, normal human aldolase B has been resolved into 5 bands. Moreover we were able to specifically stain (after isoelectrofocusing) the mutated aldolase B in livers with hereditary fructose intolerance, and to show that only the 3 most anodic bands are seen. Some different hypotheses are discussed to account for the microheterogeneity of the normal aldolase B, and for the different isoelectrofocusing pattern found in livers with hereditary fructose intolerance.


Galactose-1-phosphate uridyltransferase activities in erythrocytes from a patient with galactosemia: discrepancy between two methods.

When measuring with the spectrophotometric UDP-Glu consumption test, the galactose-1-phosphate uridyltransferase (Gal-PUT) activity in erythrocyte lysates from a 22-month-old infant with a late onset form of galactosemia was found to be approximately 25% of normal. With a radiochemical assay only a very low residual activity could be detected (+/- 1% of normal). Preincubation of the patient's lysate with purified NADase caused a marked decrease of residual Gal-PUT activity as judged from the data obtained with the consumption test. The radiochemical assay was not influenced by a similar pre-treatment. The high level of residual activity found with the consumption test in this patient was attributed to the consumption of UDP-Glu by other reactions than Gal-PUT. Because it is a direct, simple and generally applicable assay, the radiochemical procedure is suggested to be the best method for the more detailed enzymological characterisation of the Gal-PUT deficient state in galactosemics.


Bile proteins in the serum of jaundiced rats.

The major bile proteins can be detected by two-dimensional electrophoresis in the serum of cholestatic rats, three days after ligation of the common bile duct. The novel electrophoresis system used agarose gel electrophoresis in the first dimension followed by equilibrium electrophoresis in a polyacrylamide gel gradient.


[Thin-layer chromatography of sugars (author's transl)].

A thin-layer chromatographic method for the detection of sugars is described. The method can also be adapted for the use in biochemistry, pharmacology, and food chemistry. The solvent systems are: I, benzene/1-butanol/acetone/water (20 : 30 : 40 : 10, v/v); II, 1,2-dichloroethane/glacial acetic acid/methanol/water (50 : 25 : 15 : 10, v/v); III, boric acid 0.5%/1-butanol/2-propanol (20 : 30 : 50, v/v). Detection is developed by a diphenylamine aniline phosphoric acid reagent. Additionally an enzymatic method for the detection of some sugars is described.


Serum versus heparinized plasma for alanine aminotransferase and aspartate aminotransferase of normal individuals.

The influence of heparin on the estimation of aminotransferases was investigated in a reaction medium containing phosphate or Tris buffer. Heparin scarcely affects the ASAT determination, but the ALAT activity in plasma is about 70% of the activity in serum, when the enzyme determination is carried out in Tris buffer. There exists a lag phase due to which the decrease in absorbance with the incubation time is nonlinear. When the Tris buffer is omitted, the same lag phase is observed in the ALAT determination. This lag phase is not caused by the indicator enzyme LDH. Addition of phosphate to the incubation medium without any buffer abolishes this lag phase. The possibility exists that heparin influences the structure of the proteins present in plasma and that these proteins, in their turn, decrease the enzymatic activity of ALAT.


Creatine kinase B-subunit activity in human serum. II. Evaluation of s-ck b-subunit activity in the diagnosis of acute myocardial infarction.

In a group of 113 consecutive patients taken into a coronary care unit on suspicion of acute myocardial infarction, blood samples were taken every 6 h and the following enzyme activities were measured: creatine kinase (S-CK), aspartate aminotransferase (S-ASAT), alanine aminotransferase (S-ALAT) and lactate dehydrogenase (S-LD). All measurements were made according to the Recommendations of the Scandinavian Committee on Enzymes. On all patients S-CK B subunit activity was determined by immunoinhibition with a specific anti CK M-subunit inhibitory antibody. At peak values of the respective total enzyme activities CK and LD isoenzymes were further qualitatively estimated by electrophoresis. The data indicate that even serial determinations of total CK, ASAT, ALAT and LD activities in serum do not provide the information required for a conclusive diagnosis of myocardial infarction in the individual case. In contrast, the positive predictive value (PV) of S-CK B was found to be 1.0 and the negative predictive value was 0.98. S-CK MB showed a PV pos. of 1.0 and also a PV neg. of 1.0. Electrophoretic determination of S-LD isoenzymes was slightly poorer with a PV pos. of 0.96 and PV neg. of 0.98. S-CK, total activity with nearly 9 per cent false positives had a positive predictive value of only 0.91, but a negative one of 1.0.


Improved gas chromatographic analysis of chlorpromazine in blood serum.

Reliable determinations of chlorpromazine levels in blood serum samples obtained from patients were accomplished by electron capture gas chromatography. By using modifications of the procedure to insure stability of the sample, minimal losses during sample preparation and gas chromatography, and by selecting appropriate operating parameters of the electron capture detector, excellent agreement was obtained in replicate analyses with a limit of sensitivity of 1 ng/ml in 1 ml of plasma.


Effect of kininogen on the activity of the kallikreinogen-kallikrein system of human blood serum.

In experiments with kallikreinogen, kallikrein and kininogen preparations from human blood serum partially purified on QAE-Sephadex A-50, CM-Sephadex and Sephadex G-200 it was established that N-benzoyl-L-arginine ethyl ester (BAEE)-esterase activity of kallikrein and the process of autoactivation of kallikreinogen are inhibited by kininogen, especially by its high-molecular form.


Atypical GM1 ganglioside accumulation in a case of juvenile amaurotic idiocy.

The brain and liver from a 7-year-old Japanese girl with juvenile amaurotic idiocy were examined neuropathologically and biochemically. Visceromegaly and skeletal abnormalities were absent. Nerve cells in the central nervous system were swollen and contained fine fat granules. Electronmicroscopically, there were large numbers of irregular bodies in the perikarya and these corresponded to the curvilinear and membranous cytoplasmic bodies. Lipid analysis of the brain revealed that GM1 ganglioside was increased in the parietal and occipital areas, while the frontal lobe showed a normal ganglioside pattern. N-Acetyl neuraminic acid (NANA) content in all areas was not elevated. Determinations of beta-galactosidase activity were within normal ranges. The liver had no accumulation of GM1 ganglioside and showed a normal beta-galactosidase activity. These unusual findings in GM1 gangliosidosis were discussed.


[Quantitative determination of hippuric acid in urine using high pressure liquid chromatography (author's transl)].

A simple method to determine hippuric acid in urine by high pressure liquid chromatography is described. An ion exchange column is used for the separation. The detection is carried out with a photometer. The analytical criteria of the reliability of the method are tested. The results for the precision and the accuracy of the method meet the guidelines of the statistical quality control. 34 urinary constituents were tested for their interference in order to examine the specificity. Measuring urine samples from 46 normal persons yielded hippuric acid concentrations between 160 and 2010 mg/1. The median was 400 mg/1, equivalent to 357 mg/g creatinine. These results are compared to those given in the literature. Comparative investigations of those urine samples by a gas chromatographic method matched well, with a coefficient of regression of 0.86.


A quantitative assay of cortisol in human plasma by high performance liquid chromatography using a selective chemically bonded stationary phase.

The extraction and subsequent liquid chromatographic analysis of human plasma samples for cortisol is described. Extraction and chromatography are optimized, resulting in a recovery for cortisol of 96% and a detection limit of 1 microgram cortisol in 100 ml plasma. The application of two chemically modified silicas has been evaluated. The specificity of the method was tested by field desorption - mass spectrometry experiments.


Demonstration of N-dicarboxyl-mono-glycines in dicarboxylic acidurias by mass fragmentography.

Urine samples from 18 individuals with various types of dicarboxylic acidurias have been investigated by mass fragmentography for N-dicarboxyl-mono-glycines (dicarboxylglycines). One patient with methylmalonic acidemia excreted 14-20 microgram methylmalonylglycine/mg creatinine, three patients with glutaric aciduria excreted 20-60 microgram glutarylglycine/creatinine, and one patient with C6-C10-dicarboxylic aciduria excreted 120-365 microgram succinylglycine/mg creatinine. Excretion of C6-C10-dicarboxylic acids in patients with ketosis and glycogenosis and in neonates were not accompanied by excretion of C8-C10-dicarboxylglycines in measurable amounts (greater than 1 microgram/mg creatinine). Nor did patients with succinic aciduria excrete succinylglycine in amounts larger than 1 microgram/mg creatinine. On the basis of these data it is argued that production of short- and medium-chain dicarboxylglycines is not a metabolic pathway of biological significance for the elimination of short- and medium-chain dicarboxylic acids from individuals with dicarboxylic acidurias.


[The relationship between zinc levels in blood and the activity of delta-amino-levulinic acid dehydratase in human erythrocytes (author's transl)].

The blood levels of zinc, lead, copper and albumin and the activity of erythrocyte delta-aminolevulinic acid dehydratase (ALA D), with and without addition of zinc in vitro, were measured in healthy subjects and in patients with cirrhosis. In cirrhosis there was a decrease, of zinc (-40%) albumin (-38%) and of activity of ALA D (-48%) and an increase in blood lead (+80%). Correlation between these results has been studied. The increase of blood lead is probably the result of zinc decrease. Moreover, as the urinary excretion of zinc is enhanced by chelation therapy, the prescription of zinc in lead intoxication is to be recommended. The activity of ALA D in patients with cirrhosis is less enhanced by addition of zinc in vitro than is the activity in patients intoxicated with lead. Probably in cirrhosis there is especially a decrease in the synthesis of ALA D, and lead intoxication the enzyme is inhibited.


The simultaneous quantitative determination of cephalothin and cefazolin in serum by high pressure liquid chromatography.

Conventional microbiological assay procedures for cephalosporins in serum do not allow the determination of serum concentrations if more than one cephalosporin is present in a single sample. An HPLC procedure has been developed which permits the simultaneous quantitative determination of cefazolin sodium and cephalothin sodium in serum. Reverse phase chromatography using methanol in 0.2 M ammonium acetate as the mobile phase was employed to separate and quantitate the two cephalosporins in a trichloroacetic acid supernatant solution prepared from serum.


The application of an improved gas-liquid chromatographic method for the determination of the long chain non-esterified fatty acid pattern of blood plasma in children.

An accurate, practicable and fast method for the quantitative determination of the non-esterified fatty acid (NEFA) pattern in plasma is described. After extraction, thin-layer chromatography and methylation, the NEFAs are quantitated by injection on a gas chromatographic column. A precise method with a mean recovery of 96% and a coefficient variation of the total NEFA concentration between 4 and 5% has been developed by the addition of the internal standard before the extraction, the deduction of a blank value and the use of constant quantities of silicagel, taken from the thinlayer plates. The height X retention time of each methyl ester peak is calculated after injection on a free fatty acid phase (FFAP) column. The total NEFA concentration and the plasma NEFA pattern of Belgian schoolboys (15 to 17 years old) have been determined.


Pretreatment methods prior to gaschromatographic analysis of volatile fatty acids from faecal samples.

Vacuum distillation and steam distillation have been compared as pretreatment methods prior to the GC analysis of volatile fatty acids (VFA) in faecal material. Vacuum distillation resulted in a recovery range of 90-110% for all VFA in standard solutions. This was superior to the recovery ranges found after pretreatment by steam distillation. Coefficients of variance for steam distilled samples were higher than for vacuum distilled samples. Using a faecal homogenate, the vacuum distillation method was found to be highly reproducible. Spiking experiments substantiated the quantitative recovery of VFA from vacuum distilled samples. Modifications of the standard vacuum distillation procedure showed that care must be taken to ensure adequate cooling of the receiver tube.


Isoelectric focusing and hybridisation experiments on creatine kinase (EC 2.7.3.2).

In the case of increased creatine kinase levels, the MM isozyme in human serum can often be subdivided by electrophoresis into three isozymes: MM1, MM2 and MM3. This paper presents the results of hybridisation experiments, which prove the existence of two different M-subunits. The MM isozyme fractions used in the hybridisation experiments were isolated by isoelectric focusing of human sera. The experiments were completed by hybridisation of mixtures of BB and MM isozymes, leading to the formation of two MB isozymes.


Plasma short-chain fatty acids in fulminant hepatic failure.

The role of short-chain fatty acids in the pathogenesis of coma in patients with fulminant hepatic failure has been studied by gas-liquid chromatography. There was no correlation between the initial or the final plasma levels of short-chain fatty acids in these patients and the clinical outcome of their disease. A primary role for the short-chain fatty acids in the pathogenesis of coma in fulminant hepatic failure is unlikely.


Serum lecithin-cholesterol acyltransferase activity in children with familial hyperbetalipoproteinaemia.

Serum (non-fasting) was obtained from 71 healthy school children (12-14 years) and from 16 children with the heterozygous form of familial hyperbetalipoproteinaemia being treated by diet or ion-exchange resin. The activity of lecithin-cholesterol acyltransferase (EC 2.3.1.43) expressed as nmol cholesterol esterified/hour/ml serum did not change with increasing concentrations of unesterified cholesterol in the healthy children. In children with familial hyperbetalipoproteinaemia, lecithin-cholesterol acyltransferase activity was higher than in the healthy children and this activity increased with increasing concentrations of unesterified cholesterol.


Evaluation of automated glucose oxidase methods for serum glucose: comparison to hexokinase of a colorimetric and an electrometric method.

Two automated glucose oxidase methods have been evaluated with respect to accuracy, precision, recovery, linearity and various potential interferences. Trinder's method on an AutoAnalyzer II had a between-day coefficient of variation (C.V.) of 2.6% (mean 228 mg/dl), was linear to 500 mg/dl, and produced a mean recovery of 99.7%. Comparison of Trinder's method with a manual, blanked hexokinase method yielded the regression equation: TR=--1.95 + HEX (1.04); Spearman's rho correlation coefficient was: 0.974. The Beckman System I glucose method had a between-day C.V. of 1.6% (mean 198 mg/dl), was linear to 500 mg/dl, and recovered an average of 98.0% of added glucose. Comparison with the same hexokinase method yielded: SYI = 1.27 + HEX (1.02: Spearman's rho = 0.991. None of the possible interfering compounds tested caused significant deviation of results by either method within the range of concentrations encountered physiologically. Trinder's method on the AutoAnalyzer II and the System I method are accurate, precise methods and are highly recommended for routine use in the clinical laboratory.


A fluorometric assay for beta-phenylethylamine in human urine.

A sensitive and specific method for the fluorometric determination of beta-phenylethylamine (PEA) in human urine is described. PEA in urine was separated from phenylalanine and 5-hydroxytryptamine by n-heptane extraction, and determined by the ninhydrin reaction in the presence of L-leucyl-L-alanine. Using this method, the amounts of free PEA in urine samples of normal subjects and schizophrenics were measured. Normal subjects excreted 15.9 +/- 6.4 microgarm/day of free PEA, and chronic schizophrenics 9.3 +/- 2.7 microgram/day of free PEA. In normal subjects, the highest excretion of free PEA was observed in the period from 4:00 p.m. to 12:00 p.m. in a day.


Serum lipids before and after parathyroidectomy in patients with primary hyperparathyroidism.

Eight males and 36 females with hypercalcaemia were operated upon for primary hyperparathyroidism and parathyroid adenomata were revealed in every case. The serum levels of cholesterol and triglycerides were determined before the operations and 6,12 and 18 months after them. Furthermore, the serum lipids of the patients were compared with those of a normacalcaemic sex- and age-matched control group. The serum cholesterol concentration in primary hyperparathyroidism was about 8-10% lower in both females and males compared with the correspondeing control cases and the levels of serum trigycerides were about 22% and 60% lower. After operation the serum cholesterol concentration returned to a normal level and the triglycerides nomalized. The results are discussed in the light of present knowledge about dietary calcium intake, primary hyperparathyroidism and lipid metabolism.


Dihydroxanthopterinuria in phenylketonuria and lethal hyperphenylalaninemia patients.

7,8-Dihydroxanthopterin in identified in urine from phenylketonuria and lethal hyperphenylalaninemia patients. Because 7,8-dihyroxanthopterin is readily oxidised to xanthopterin, most of the characterisation was performed on xanthopterin. This finding indicates a gross disturbance of tetrahydrobiopterin metabolism in these patients. 7,8-dihydroxanthopterin or a related pterin may play a role in the pathogenesis of neurological symptoms in phenylketonuria and lethal hyperphenylalaninemia.


Human calcitonin radioimmunoassay: characterization and application.

A radioimmunoassay of human calcitonin (HCT) has been developed, employing antibodies formed in response to a HCT-bovine gamma globulin conjugate. The assay is sensitive (lower limits of detection 30 pg/ml serum), reproducible, and specific for intact HCT and carboxyl-terminal fragments of HCT. Serum HCT was detected in 76% of 63 normal subjects (mean +/- S.E.M. = 72 +/- 7 pg/ml), and was increased in cord sera, as well as sera from patients with chronic renal disease and medullary thyroid cancer. Increased levels were observed during calcium infusion into normal subjects, but not in sera from pregnant women or subjects with chronic hypercalcemia. No significant correlation was observed between serum ionized calcium and HCT in sera from 147 hospitalized patients. These findings suggest the usefulness of this assay for further studies of conditions affecting calcitonin homeostasis.


Carrier detection in X-linked recessive (Duchenne) muscular dystrophy: pyruvate kinase isoenzymes and creatine phosphokinase in serum and blood cells.

Allosterism allows individual assay of both isoenzymes, one abundant in muscle, of pyruvate kinase (PK), recently reported superior to serum creatine phosphokinase (CPK) in detecting patients with and female carriers of X-linked recessive (Duchenne) muscular dystrophy (DMD). Extensive comparative studies did not support these findings and confirmed the marked superiority of CPK over rariants of PK or other enzymes in sensitivity, stability and convenience. Deducting the adenylate kinase increment (AKI) further refined the CPK assay, eliminating the effect of haemolysis in diagnosis and enabling studies of blood cell content. Both leucocytes and erythrocytes liberated PK and lactate dehydrogenase (LDH) after brief chilling or disruption. Only erythrocytes showed a CPK content, however, constantly adjusted to match that of serum as if by free cell membrane passage, but less accomodating to a sudden large influx of CPK than of LDH, where an apparent buffering effect could account for differences in clinical response.


Kinetics of intravenous administered L-phenylalanine in patients with cirrohosis of the liver.

The metabolism of intravenously administered L-phenylalanine has been studied in 13 patients with cirrhosis of the liver and in 17 control subjects. The decline in the plasma phenylalanine concentration followed a biexponential curve and the kinetics could be evaluated assuming a two-compartment model. The volume of the central compartment was reduced in the cirrhotic patients, reflecting a diminished liver pool size. The total phenylalanine clearance was lower in the cirrhotic patients, due mainly to a reduction of the liver cell mass or to changes in the intrahepatic membrane permeability and only to a minor extent to a reduced hepatic blood flow. The elimination rate constant from the central compartment was similar in both groups, suggesting that the remaining liver cells, had a normal capacity to hydroxylate phenylalanine to tyrosine. There was considerable overlapping in the kinetic parameters between the two groups, and even in patients with well established cirrhosis an apparently normal phenylalanine metabolism was observed.


Sulfhaemoglobin. Absorption spectrum, millimolar extinction coefficient at lambda = 620 nm, and interference with the determination of haemoglobin and of haemiglobincy anide.

The spectrophotometry properties of sulfhaemoglobin (SHb) and some derivatives were investigated using an improved technique for measuring the SHb fraction induced in human blood samples. The millimolar extinction coefficient of SHb at lambda = 620 nm was found to be 20.8 (S.D. 1.48; S.E. = 0.44; n = 11). In addition it was demonstrated that the spectral changes occurring in SHb containing haemoglobin solutions upon the addition of KCN, K3Fe(CN)6 and K3Fe(CN)6 +KCN invalidate the KCN addition method for the determination of haemiglobin. The influence of clinically occurring SHb fractions on the internationally standarized total haemoglobin determination were shown to be insignificant.


The occurrence of 2-hydroxyisovaleric acid in patients with lactic acidosis and ketoacidosis.

Examination of urine samples by capillary column gas chromatography and mass spectrometry showed the presence of 2-hydroxyisovaleric acid together with trace amounts of the three branched-chain 2-keto acids in five patients with lactic and ketoacidosis. None of these compounds was detected in urine from healthy controls.


An immobilized hexokinase enzyme stirrer for a simple and economical assay of plasma glucose.

We have adapted the hexokinase glucose procedure to an immobilized enzyme stirrer for the determination of glucose concentrations in human blood plasma. The procedure is a fluorometric rate method measuring the formation of NADPH catalyzed by immobilized glucose-6-phosphate dehydrogenase and hexokinase held within a tiny stirrer. The enzyme stirrer is stable for at least two months and can be used over eight-hundred assays without any loss of activity.


The presence of immunoreactive growth hormone release-inhibiting hormone in normal cerebrospinal fluid.

Immunoreactive GHRIH is present in normal CSF at a level of 55 +/- 28 pg/ml. Immunoreactivity shows mobility identical to synthetic GHRIH standard on sephadex and thin layer chromatography, and can be removed by antibody conjugated to sepharose.


Increasing growth with raised circulating somatomedin but normal immunoassayable growth hormone.

Two patients are described with elevation of circulating somatomedin A concentration but normal growth hormone levels. One,a young male, appeared clinically acromegalic; the other, a young female, was tall with kyphoscoliosis, and her appearance resembled Marfan's syndrome. In both patients plasma growth hormone concentration was suppressible by hyperglycaemia. It is suggested that their clinical syndromes resulted from excessive somatomedin activity.


Oestrogen-progestogen oral contraceptives and urinary calcium excretion.

To examine the effects of age and use of oestrogen-progestogen oral contraceptive agents (OCA) on urinary calcium excretion, 24 h urine collections were obtained from 525 women aged 16-69 years during a health survey, and measurements made of the amounts of calcium, creatinine, sodium, potassium and magnesium excreted. Younger women using OCA excreted more potassium and creatinine but less calcium, and less calcium and magnesium relative to creatinine, than corresponding controls using no OCA. Older women excreted less creatine, but significantly greater amounts of calcium, sodium, potassium and magnesium relative to creatinine than younger women. It is postulated that the diminished urinary calcium excretion observed in women using OCA resulted from suppression of bone resorption by oestrogens in OCA.


Prevention by somatostatin of rise in blood pressure and plasma renin mediated by beta-receptor stimulation.

The interrelationships of increased plasma renin and elevated blood pressure following acute beta-stimulation by orcipernaline and its prevention by somatostatin was studied in normal man. During somatostatin infusion basal values of renin and blood pressure were unchanged. Following orciprenaline both variables increased significantly. Combination of somatostatin and orciprenaline reduced the rise in plasma renin activity by 49%, mean arterial blood pressure by 21% and heart rate by 19%, compared with beta-stimulation alone. The results indicate that the inhibitory action of somatostatin on plasma renin activity may be mediated via beta-receptors. The lesser increase of blood pressure under somatostatin plus orciprenaline also indicates a possible inhibitory effect of somatostatin on beta-adrenergic receptors.


Glutathione alterations in rat liver after acute and subacute oral administration of paracetamol.

1. The effect on hepatic glutathione was studied in rats pretreated orally with various dosages of paracetamol (acetaminophen) for varying time intervals. 2. Paracetamol caused a dose-dependent depletion of hepatic glutathione, the maximum depletion occurring 3 h after acute dosing, the levels returning to normal by 12 h after low doses (0-1 or 0-25 g/kg, p.o.) and by 72 h after the highest doses (1 g/kg, p.o.). 3. Before returning to normal, the liver glutathione levels became significantly greater than the control values (35-40%) at 24 and 48 h in 0-5 and 1 g/kg paracetamol-treated rats, respectively, suggesting thereby a 'glutathione rebound action' of paracetamol-pretreatment. 4. In contrast with the acutely treated rats, the liver glutathione content remained unchanged when 0-5 g/kg paracetamol was administered twice daily for 7 consecutive days. 5. Fasting caused a significant reduction in hepatic glutathione, the glutathione stores were replenished within 6 h after feeding. 6. The results suggest that the hepatic glutathione levels are reversibly depleted by single large doses of paracetamol, while the glutathione depletory effect appears to decrease after the repeated administration of this hepatotoxic agent.


Unusual effect of some alpha-mercaptoacrylic acids on metabolism of zinc in the rat.

1. Gavage of rats with beta-aryl derivatives of alpha-mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten-fold increases above normal zinc levels were attained 2-8 h after doses of 50 mg/kg of the phenyl and furan derivatives. 2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma. 3. Close to 100% of the zinc and of the alpha-mercapto-beta-(2-furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules. 4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein. 5. These compounds appear to mobilize zinc from tissue stores and retard zinc clearance from plasma.


Blockade by phentolamine of the potentiation of histamine-induced vasoconstriction caused by serotonin and methysergide in the rabbit ear artery.

1. In subconstrictor doses, both serotonin and methysergide potentiated the vasoconstrictor responses to histamine in the isolated artery of the rabbit ear. 2. In the presence of phentolamine (5 microgram/ml) the potentiating actions of serotonin and methysergide were significantly reduced. 3. This blocking action of phentolamine could be overcome by increasing the concentration of serotonin or by washing the preparation. 4. In arteries taken from rabbits pretreated with reserpine, serotonin still potentiated the response to histamine and phentolamine still blocked this potentiation. 5. The concentration of phentolamine required to block potentiation also blocked the direct constrictor response to serotonin. It did, however, produce a significantly greater blockade of the vasoconstrictor response to noradrenaline. 6. The results indicate that the action of phentolamine in blocking the vascular potentiation produced by serotonin and methysergide is not due to a blockade of alpha-receptors.


The participation of enteric inhibitory nerves in accommodation of the intestine to distension.

1. The amounts by which various weights distended isolated segments from the distal colons of guinea-pigs were measured. 2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect. 3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accomodation of the intestine to stretch.


Dialysis in the treatment of renal failure in patients with liver disease.

The value and effects of treating renal failure by dialysis are analyzed in a series of 84 patients with various types of liver disease. Although none of the 25 patients with cirrhosis survived, six of 50 with fulminant hepatic failure recovered completely as did seven of nine patients with renal failure secondary to extrahepatic biliary tract obstruction or with liver and renal damage following episodes of severe hypotension. Dialysis was required for seven weeks before diuresis occurred in one patient in the latter group. Both peritoneal and hemodialysis satisfactorily controlled plasma urea and creatinine levels, except in patients with fulminant hepatic failure in whom this was only achieved by hemodialysis. Complications of dialysis were most common in patients with cirrhosis and fulminant hepatic failure and included hypotension, gastrointestinal bleeding, and intraperitoneal sepsis. Overall, the results show that dialysis is only worth attempting in those patients in whom recovery of the underlying liver lesion is possible, and even then treatment for prolonged periods may be necessary.


Improved growth in growth retarded uremic rats with use of calorie supplementation.

Renal failure in childhood is often associated with poor growth. Growth in uremia was studied using young growing male Sprague-Dawley rats made moderately uremic (SUN77 mg/100 ml) by partial nephrectomy. Uremic rats weighed less than control rats after 17 days of observation (P less than .01). Uremic rats supplemented by corn oil gavage had significantly better weight gain than nonsupplemented uremic rats (P less than .005). Uremic rats whose appetite was stimulated by the addition of saccharin to diet also had significantly better daily weight gain than uremic rats not having saccharin added to diet (P less than .05). Calorie intake appeared to be the limiting variable with regard to observed differences in growth. In fact, when adjusted for calorie intake/weight-75, uremic rats did not differ from control rats in weight gain/weight-75. In addition, control rats fed diets identical to those consumed by uremic rats grew equally as poorly. Improved growth in uremic rats with calorie supplementation was felt to be real growth in that body composition studies showed proportionate gains in cell mass, total body solids, liver and muscle. Catch-up growth was not observed, perhaps because insufficient supplemental calories were provided or because other unexplained factors contributed to growth retardation.


Formation of a ternary complex with serum albumin: an explanation for the effect of alpha-mercapto-beta-(2-furan) acrylic acid on rat plasma zinc clearance.

1. Four, six and eight hours after gavage of rats with alpha-mercapto-beta-(2-furan)acrylic acid (MFA) (25 mg/kg) serum zinc concentration was increased ten-fold over control levels and a mean molar ratio of 1 albumin:0-4 zinc:0-8 MFA was found for seventeen sera. 2. At pH 7-5 a maximum of 1 mole of MFA could be bound per mole of metal-free bovine serum albumin. 3. In the presence of zinc ion, albumin-zinc-MFA complexes formed, since for each mole of albumin-zinc complex an additional mole of MFA could be bound to albumin. Complexes up to a molar stoichiometry of 1 albumin:2 zinc:3 MFA were prepared. 4. MFA stabilized the albumin-zinc complex against dissociation. 5. Formation of similar complexes in vivo may account for the markedly delayed clearance of plasma zinc rats administered beta-aryl derivatives of alpha-mercapto-acrylic acid.


Hypersequestration of 51Cr-labelled erythrocytes as a criterion for splenectomy in regular hemodialysis patients.

The splenic uptake of 51Cr-labelled autologous erythrocytes was studied by body surface counting in 20 hemodialysis patients. Evidence for splenic hypersequestration of erythrocytes was obtained in 7 patients. Splenectomy was performed in 6 of these and led to a reduction in transfusion requirements. One patient without evidence of splenic hypersequestration of red cells was also subjected to splenectomy but was not improved. The importance of following the splenic uptake of 51Cr for a sufficiently long time to detect a delayed uptake of 51Cr is pointed out.


Cardiovascular effects of amitriptyline in anaesthetized dogs.

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/dg) amitryptyline caused small increases in heart rates, contractility, blood pressure, coronary blood flow and aortic flow. 3. Large doses produced initial depressant effects on myocardial reflex rises in these and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in ortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.


The effect of chromatographically pure sample of adenosine 5'-tetraphosphate on sheep and rabbit blood platelets.

1. The commercially available trisodium salt of adenosine 5'-tetraphosphate (ATetraP) (Sigma) was found to be contaminated with ATP, ADP and AMP, and therefore unsuitable for use in platelet studies. 2. The more stable barium salt of ATetraP was converted to the ammonium salt and found to be chromatographically homogeneous. This sample was tested for its influence on sheep blood platelets in citrated-rich plasma by the photometric method. 3. The ammonium salt of ATetraP (5-105 mumol.1(-1)) induced platelet aggregation which showed no tendency towards disaggregation. 4. The log dose-response lines for ATetraP and for adenosine diphosphate were parallel. On a molar basis, the tetraphosphate and only 1.5% of the aggregating activity of ADP. 5. The initial rate of aggregation induced by the tetraphosphate was inhibited by adenosine 5'-monophosphate analogues which are selective ADP-antagonists. These compounds also dispersed aggregates produced by ATetraP. 6. Platelets made refractory to ADP were also refractory to ATetraP. 7. Like ADP, ATetraP induced the change in shape of rabbit platelets and in this respect had only 3.4% the activity of ADP. 8. It is concluded that ATetraP per se can induced platelet aggregation and platelet shape change, and appears to exert its effect at the same site on the platelet surface as does ADP.


The size of the juxtaglomerular apparatus in diabetic glomerulosclerosis and its correlation with arteriolosclerosis and arterial hypertension: a morphometric light microscopic study on human renal biopsies.

The surface areas of the juxtaglomerular cell complexes and the index of arteriolar sclerosis were evaluated in renal biopsies from 50 patients with diabetic glomerulosclerosis. The mean surface areas of the JGC's were significantly enlarged compared to that of normal renal tissue, whereas no significant difference could be found between kidneys from hypertensive and the normotensive diabetics. A positive linear correlation was found between mean JGC-size and the index of sclerosis of the afferent arterioles. This was interpreted as the result of faulty coordination between the activity of the juxtaglomerular apparatus and the systemic arterial blood pressure. This is caused by stenoses of the preglomerular afferent arterioles in diabetic arteriosclerosis.


Hemodynamic evaluation of hypotension during chronic hemodialysis.

Hypotensive episodes occur frequently during hemodialysis; they are often sudden and difficult to prevent despite careful clinical control. Their etiology was studied by investigating the hemodynamic response of five patients submitted to ultrafiltration during their three first dialyses. A Swan Ganz catheter was inserted and left in position for 5 days. Simultaneous determination of cardiac output, mean pulmonary artery (PAP) and capillary and systemic arterial pressures were recorded. 10 hypotensive episodes were observed. In 3 patients in whom the first hypotensive episode occurred 10 minutes after the start of dialysis, there was a significant drop in PAP, cardiac index and stroke index while heart rate and peripheral resistance remained unchanged. Paradoxical bradycardia was observed. In 4 patients hypotension was observed more than one hour after initiation of dialysis. Before the hypotensive episode there was moderate elevation of heart rate and peripheral resistance and an insignificant reduction in PAP. Cardiac index and stroke index were diminished. The decrease in MAP was only 2 mm Hg. Hypovolemia is the most important factor in hemodialysis-induced hypotension but other factors such as vagal stimulation, autonomic neuropathy and osmotic disequilibrium can interfere with blood pressure control and trigger hypotension. Methods of preventing hypotension during dialysis, including the infusion of low molecular weight dextran, are discussed.


Malignant hypertension and uremia in scleroderma: efficacy of nephrectomy and hemodialysis.

Two cases of scleroderma are presented in which malignant hypertension developed abruptly, accompanied by rapidly progressive renal failure. The malignant hypertension was associated with high plasma renin levels and like other forms of hyperrenninemic hypertension and uremia, was refractory to both antihypertensive medication and extracellular fluid volume control with hemodialysis. Blood pressures became controllable only after bilateral nephrectomy was performed, and in each case resulted in a reversal of a rapidly progressive downhill course. Though both patients had multisystem involvement at the onset of renal failure, the non-renal manifestations of scleroderma have not progressed rapidly. Consequently, when patients with scleroderma develop malignant hypertension and uremia, aggressive therapy with dialysis and nephrectomy may significantly prolong survival.