Management of preinfarction angina. Evaluation and comparison of medical versus surgical therapy in 43 patients. Short-term results of aggressive surgical management were compared with results of medical management in forty-three patients with preinfarction angina admitted to the coronary-care unit (CCU) over an 18 month period. These patients were selected from 1,609 consecutive admissions to the CCU because they met strict criteria for preinfarction angina: severe chest pain at rest, ST-segment elevation or depression during pain which subsided rapidly after cessation of pain, and normal serum enzymes (CPK, SGOT, and LDH). Twenty-three patients had coronary angiography, done with operating room and pump standby. One patient, who had total occlusion of the left main coronary artery, died during the study. Twenty-one of the remaining patients were considered surgical candidates, and were treated immediately after angiography with 1 to 3 vein bypass grafts. There was one late postoperative death and, of the 20 survivors, 2 had ECG evidence of acute myocardial infarction and one had mild angina at time of discharge. In contrast, of the 21 patients treated medically, 13 sustained acute MI, resulting in 8 instances of congestive heart failure and 4 cases of ventricular fibrillation. Four patients died in cardiogenic shock. With the use of rigid criteria, a small subgroup of patients with variant angina at high risk of developing AMI has been identified and categorized as having preinfarction angina. Our experience suggests that aggressive surgery immediately following coronary angiography offers a lower incidence of MI, morbidity, and death than does medical management.


Mitral atresia with premature closure of foramen ovale. A rare hemodynamic cause for failure of Blalock-Taussig anastomosis to relieve inadequate pulmonary blood flow. The clinical, hemodynamic, and surgical findings encountered in the management of a hypoxic male infant with a rare and complex variety of cyanotic congenital heart disease associated with inadequate pulmonary blood flow are described. A poor clinical response to creation of a Blalock-Taussig anastomosis led to the discovery of mitral atresia complicated by premature closure of the foramen ovale and partially relieved by the presence of a levoatriocardinal vein. The subsequent creation of an atrial septal defect enhanced the function of the subclavian artery to pulmonary artery anastomosis and provided palliative relief of hypoxia. Some of the clinical and laboratory findings indicating the presence of additional lesions complicating the picture of a tetralogy of Fallot and requiring additional surgical considerations are discussed. The experience indicates that hemodynamic as well as surgical causes may explain the failure of a systemic artery to pulmonary artery anastomosis to function adequately and should be sought.


Hemodynamic evaluation of the Lillehei-Kaster pivoting disc valve in patients. Forty-five patients with Lillehei-Kaster pivoting disc valves had intraoperative assessment of valve hemodynamic function by simultaneous recording of aortic, left ventricular, and left atrial pressures and cardiac output. Mean transvalve gradients and prosthetic valve areas were calculated and recorded. Comparison of the results with data previously reported on the caged-ball valves indicates that the Lillehei-Kaster pivoting disc valve has superior hemodynamic characteristics.


Complete correction of double-outlet right ventricle with situs inversus, 1-loop, and 1-malposition (I,L,L) with subaortic VSD and pulmonary stenosis. The repair a unique case of double-outlet right ventricle is reported. This case illustrates the increasingly difficult problem of developing an appropriate nomenclature in complex congenital heart disease. A classification of double-outlet right ventricle based upon Van Praagh's symbolic terminology is suggested.


Malfunction of tricuspid valve prosthesis shown by isotope angiocardiography. Isotope angiocardiography established prosthetic tricuspid valve obstruction in a patient 6 years after triple valve replacement. Thrombus formation is a common complication of prosthetic cardiac valves, particularly in the tricuspid position where engagement of cage with myocardium is an additional potentially obstructive hazard. Comparison is made between the information yield of the isotope investigation and cardiac catheterization with contrast cineangiography. It is suggested that the isotope technique can noninvasively provide valuable anatomic and functional data, particularly where the right side of the heart is to be examined.


Subclavian-coronary artery anastomosis. A technique for definitive correction of anomalous origin of left coronary artery. A case of anomalous origin of the left coronary artery from the pulmonary artery in a 5-year-old child is presented. Surgical correction by means of a direct subclavian-coronary anastomosis was performed at normothermic temperatures without cardiopulmonary bypass. Pre- and postoperative studies including angiography are presented. The rationale for this approach and its benefits are compared to previously utilized surgical techniques. We feel that this method is superior in that it creates a two-coronary system without utilizing prosthetic or vein bypass grafts. It thus can be used in infancy, allows for future growth and development, and is not subject to the inherent deficiencies of prosthetic or vein grafts. All 4 known cases of subclavian-coronary anastomosis previously reported are discussed.


Correction of Type C complete atrioventricular canal. Surgical considerations. Case histories of 8 consecutive patients who underwent surgical correction of Type C complete atrioventricular (A-V) canal at the Ochsner Medical Center over the past 2 years were analyzed. Ages ranged from 1 1/3 to 14 years. Before bypass, the level to which the common leaflets ascend and the arc that they inscribe are determined by palpation to ensure their proper reconstitution on the canal patch. The major area of closure is usually allocated to the ventricular portion. Mapping the conduction system and tying sutures with the heart beating in high-risk conduction areas prevent heart block. Precise marking and splitting of the valve leaflets and reattachment with interrupted felt-buttressed sutures avoid disruption. All patients survived the operation and have shown clinical improvement. At recatheterization, 7 of 8 patients have shown a definite decrease in mitral insufficiency. Right ventricular pressures returned toward normal and there were no significant residual shunts. Associated anomalies or previous operations have not been a contraindication, and since we have begun using the present technique, we have achieved consistently good results without prosthetic valves.


A new surgical approach for correction of partial anomalous pulmonary venous drainage into the superior vena cava. Nine children with partial anomalous pulmonary venous drainage into the superior vena cava were operated upon. The technique consisted essentially of partitioning and enlargement of the superior vena cava. The partitioning was done in all but one patient, with a longitudinal suture starting above the highest pulmonary vein directing the pulmonary venous flow through the enlarged atrial septal defect into the left atrium. The anterior cavo-auricular tunnel was enlarged with a right atrial appendage-superior vena cava angioplasty. Follow-up studies were done between 1 and 3 years after surgery. The hemodynamic data were normal in 7 patients. In 8 children, the superior vena cava was unobstructed and its diameter was normal as demonstrated by cavograms. In all patients, the angiographic evaluation of the pulmonary venous return was normal. These results are encouraging and indicate that this new approach is superior to those which have previously been reported.


Bypass of the right and circumflex coronary arteries with the internal mammary artery. Our experience with the internal mammary artery (IMA) for coronary bypass grafting in the past 3 years includes 323 grafts in 253 patients. After an initial group of IMA to left anterior descending (LAD) coronary artery grafts, we began using the IMA to bypass circumflex and small right coronary arteries (RCA). This report describes our experience with IMA bypass of coronary vessels other than the LAD. A total of 96 patients have had an IMA graft to the circumflex or RCA. Most of these patients had two or more bypasses. The mortality rate for this group has been 7 per cent, 7 of 96 patients. Postoperative angiography in 82 of 89 survivors has shown a patency rate of 98 per cent in 83 of 85 grafts studied. We conclude that the IMA is the vessel of choice for coronary artery bypass and that it can be used to bypass any of the main coronary arteries.


Cricothyroidotomy: elective use in respiratory problems requiring tracheotomy. Surgical teachings insist that cricothyroidotomy should be performed only under emergency conditions as a temporary means of securing an airway. Subsequent subglottic stenosis is thought to occur in alarming numbers of patients intubated for any length of time. The incidence of complications associated with cricothyroidotomy has not been critically examined since Jackson's classic paper in 1921, condemning the operation. A total of 655 patients with cricothyroidotomy tubes in place from hours to months were studied to determine the incidence of problems associated with this procedure. The over-all complication rate was 6.1 per cent. There was one cricothyroidotomy-associated death. Chronic subglottic stenosis did not occur, although 5 patients required resection of tracheal strictures. No additional complications occurred if the procedure was carried out at the bedside instead of in the operating room. The simplicity, absence of cross-contamination of median sternotomy incisions, and safety documented by this study recommend routine use of cricothyroidotomy in patients whose management requires tracheotomy.


Epidural anesthesia following thoracotomy in patients with chronic obstructive airway disease. Epidural analgesia for control of postoperative thoracotomy pain in patients with carcinoma of the lung and chronic obstructive airway disease is described. The rationale and procedure for its use are presented. Epidural analgesia used in 8 patients requiring pulmonary resection who had chronic obstructive airway disease resulted in an improved postoperative course and avoided use of narcotics or a respirator in 7 of the 8 patients.


Systemic air embolism: does it occur after experimental penetrating lung injury? Systemic arterial air embolization following penetrating injury of the lung has been previously reported. As we had not recognized this complication clinically, we studied this problem in 11 healthy dogs. In each of them, a mock circulation was created by establishing two central external arteriovenous shunts with transparent plastic tubing in which air bubbles could be seen. Also, a Doppler flow detector capable of sensing intravascular air was attached to a carotid artery. Systemic arterial and pulmonary capillary wedge pressures were recorded, and a standard lung laceration was produced. In 5 of the dogs, in addition, tension pneumothorax was induced by injection of air into the pleural space. The dogs were monitored for intravascular air for 15 minutes before and after the induction of hypotension by withdrawal of blood from the shunts. In no animal was air seen in the shunts, nor was there the characteristic deflection of the Doppler seen with intravascular air, although the preparation was sensitive to the detection of as little as 1 ml. of air injected into the left atrium. These observations lead us to question whether arterial air embolism occurs with penetrating pulmonary trauma in man.


Etiology, incidence, and prognosis of renal failure following cardiac operations. Results of a prospective analysis of 500 consecutive patients. A prospective study of 500 consecutive patients surviving the first 24 hours following cardiac surgical procedures was undertaken to determine the prevalence, etiology and results of therapy for postoperative acute renal failure (ARF). Thirty-five patients developed either moderate or severe ARF and an additional 102 developed mild preprenal azotemia. Positive risk factors noted inthe development of postoperative renal failure included age, elevated preoperative concentrations of blood urea nitrogen (BUN), serum creatinine, and decreased 24 hour urine creatinine clearance. The duration of cardiopulmonary bypass (CPB), aortic cross-clamping, and the total duration of the operation also closely correlated with the incidence of ARF. In the early postoperative period, clinical assessment of hemodynamic change was most helpful in predicting postoperative ARF. Significant negative risk factors included type of operation performed, New York Heart Association classification, the use of preoperative diuretic therapy, and associated other chronic illnesses. During the operation itself, the lowest and mean blood pressures, flow rates on CPB and the presence of hemoglobinuria failed to correlate with subsequent ARF. The mortality rate for established ARF was extremely poor (88.8 per cent), and there were no survivors among those requiring dialysis. ARF following cardiac surgery is a highly lethal complication which arises in a setting of inadequate cardiac function and is associated with a multiple organ system failure. Therapy of this postoperative complication, therefore, appears to be better directed toward its prevention rather than treatment once established.


Late results of surgery for left ventricular outflow tract obstruction in children. Forty-four patients, with a mean age at surgery of 10 years, were followed for 5 to 16 years (mean 9.7 years) after relief of left ventricular outflow tract obstruction. There were no early deaths, but 5 late deaths occurred, 3 following reoperation. Twenty-five patients were recatheterized from 1 to 16 years later (mean 6.6 years). In 21 of 32 patients (66 per cent), a new diastolic murmur followed relief of valvular stenosis; 25 (78 per cent) of these patients had a postoperative diastolic murmur. Seventeen of these 25 (68 per cent) were recatheterized, and 11 of the 17 (65 per cent) had moderate-to-severe aortic incompetence on angiography. Eight patients (18 per cent) have undergone reoperation and 9 more (20 per cent) will have to be reoperated upon soon. Although the aortic valve gradient and left ventricular stroke pressure were reduced in all obstructive types after surgery, left ventricular end-diastolic pressure significantly increased and cardiac index decreased after valvotomy. Cardiomegaly and electrocardiographic (ECG) abnormalities were present in 45 and 66 per cent, respectively, of all postoperative patients. Although 93 per cent of patients may be expected to survive and 82 per cent be reoperation free at 10 years, further surgery thereafter becomes increasingly common. Timely relief of obstruction prevents sudden death and produces excellent symptomatic improvement, but the operation is only palliative. Development of a reliable pediatric valve and ventriculo-aortic conduit may encourage earlier and more aggressive therapy.


Occipital alopecia following cardiopulmonary bypass. Postoperative alopecia is a minor complication of surgery but a cosmetic disaster to the patient. Over a 3 year period, 60 cases of occipital alopecia were discovered in patients following open-heart surgery and 5 cases on other surgical services. In contrast to previous reports, 29 patients had alopecia one year later, presumed to be permanent. Extensive operations, with prolonged recovery and elective overnight mechanical ventilation, were common to all. Retrospective analysis and prospective studies clearly demonstrated that localized scalp pressure was the cause of the alopecia and that the duration of pressure determined the extent of the damage. Moving the patient's head at regular intervals during operation and recovery eliminated the alopecia. The type of head rest used did not modify the development of alopecia. Electrical injury and the use of heparin, hypothermia, electrocautery, or hypotension were eliminated as possible causes. Conclusive evidence correlating periperative events with the formation of pressure sores in man has not been previously reported.


Surgical treatment of unstable angina by saphenous vein and internal mammary artery bypass grafting. During a 3 year period, direct myocardial revascularization was performed on an urgent basis in 48 patients with intermittent resting chest pain which persisted more than 24 hours despite in-hospital medical therapy and was accompanied by electrocardiographic changes representative of ischemia. Sixteen patients had saphenous vein (SV) grafts exclusively, and 32 patients each had one or two internal mammary artery (IMA) grafts with or without additional vein grafts. Follow-up ranges from 5 to 41 months (mean, 22 months). Twelve patients had single grafts to the left anterior descending coronary artery (LAD), 18 had double grafts, 16 had triple grafts, and 2 had quadruple grafts. The LAD required grafting in every patient. There was one operative death (2 per cent) and one late death from noncardiac causes. There were two (4 per cent) early postoperative myocardial infarcts and no late infarcts. Actuarial analysis projects a survival rate of 96 per cent 3 years postoperatively. Eighty-one per cent of the survivors are in Functional Class I, 17 per cent are in Class II, and 2 per cent are in Class III. All patients had postoperative angiography 2 weeks after operation. Eighty-six per cent of the SV grafts and all IMA grafts were open. No significant differences were observed between mean preoperative and postoperative left ventricular end-diastolic pressures or ejection fractions, but these parameters were noted to improve after operation in several patients. The remarkably high early and late survival rates, the low incidence of myocardial infarction, and the excellent functional results after rather long follow-up indicate that emergency coronary revascularization provides an effective therapy for unstable angina. The use of IMA grafts, when feasible, is a safe and possibly preferable approach in these patients.


Successful repair of double-outlet right ventricle with bilateral conus, 1-transposition of great arteries (S,D,L), and subpulmonary ventricular septal defect. Surgical correction was carried out successfully in a severely cyanotic 3-year-old Japanese girl who had a very rare type of double-outlet right ventricle. The malformation was associated with bilateral conus, 1-transposition of the great arteries, and subpulmonary ventricular septal defect without significant pulmonary stenosis in situs solitus. A large amount of subaortic conal musculature which separated the aortic valve from the subpulmonary ventricular septal defect was removed, as was the anterior rim of the ventricular septal defect. A tunnel, constructed with a woven Teflon prosthesis, was inserted in such a manner as to direct blood from the left ventricle through the defect and out to the aorta. The pulmonary outflow tract was reconstructed with a Teflon patch lined with pericardium. The patient's postoperative recovery was uneventful, and she was doing well 3 months postoperatively. To our knowledge, no identical case with a similar type of surgical correction has previously been reported.


Nonoperative management of late failure of a Glenn anastomosis. Transvenous wafer occlusion of patent superior vena cava--right atrial junction. A case is presented illustrating delayed failure of a right Glenn anastomosis due to patency of the superior vena cava-right atrial (SVC-RA) junction. Clinical deterioration was rectified by a unique nonoperative approach. A transvenous catheter was designed, constructed, and used to accurately place an umbrella-like occlusive wafer at the SVC-RA junction. In this manner the integrity of the cavopulmonary shunt was re-established. A gratifying and uncomplicated palliation has thus far been achieved.


Left ventricular--right atrial shunt: an unusual cause of hemodynamic deterioration following aortic valve surgery. Two cases of left ventricular-right atrial shunts inadvertently produced during aortic valve replacement are described. It is surprising that this complication is not more prevalent considering the close proximity of the aortic and mitral valves to the atrioventricular portion of the membranous septum. A left-to-right shunt should be a consideration in patients who fail to improve following aortic valve surgery, especially if the valve and subaortic region were heavily calcified or septal trauma occurred during the surgical procedure.


Repair of ventricular septal defect after pulmonary artery banding. Since 1964, 90 patients have undergone two-stage surgical repair of ventricular septal defect (VSD) with pulmonary artery banding (PAB) in early infancy and total repair at an average age of 4 years. Reconstruction of the pulmonary artery was accomplished with a pericardial patch, woven Dacron patch, or transverse angioplasty. The VSD was closed with a knitted Dacron patch in 75 patients and by primary suture technique in 13 patients. The VSD closed spontaneously in 2 patients. The mortality rate for patients who had repair and debanding was 9 per cent (8 patients), including 4 deaths due to severe pulmonary hypertensive disease, 3 from congestive heart failure, and one from atrioventricular block. Twenty patients underwent repeat cardiac catheterization several months to 7 years after total repair. This study revealed no shunt in 16 patients and a minimal shunt not requiring operation in the other 4 children. Slight residual stenosis of the pulmonary artery was found in 2 patients and a residual infundibular stenosis in another 2 patients. We believe two-stage surgical treatment of VSD in severely ill infants under one year of age is safe and reliable.


Secundum atrial septal defect encountered in infancy. From 1953 to 1972, approximately 170 patients less than 16 years old were seen at the Mayo Clinic for isolated secundum atrial septal defect. Thirteen of these patients were initially seen when they were less than 2 years old. Eleven of the patients had symptoms, and one of these died. Four patients failed to respond to medical management and underwent successful repair of their defects before they were 2 years old. Infants with isolated secundum atrial septal defect and significant symptoms are at an increased risk of death. Consideration should be given to early surgical closure of the defect in those infants who do not respond promptly and completely to medical therapy. Surgical repair in infancy can be accomplished with minimal risk and excellent early and long-term clinical results.


Aneurysm of the membranous ventricular septum. Surgical consideration and experience in 29 cases. Twnety-nine cases of aneurysm of the membranous septum in association with various cardiac abnormalities are described. These aneurysms are more common than has been previously thought (10% of the total associated anomalies managed surgically). The patients' ages ranged from 3 months to 28 years. All of the 29 patients were divided into three groups. Group I consisted of 15 patients with ventricular septal defect (VSD), 5 of whom had associated artrial septal defect (ASD). Group II consisted of 5 patients with VSD and pulmonic obstruction, and Group III comprised 9 patients with transposition of the great arteries (TGA). Complete correction was performed in all the patients, and the aneurysm was imbricated in the suture line of the VSD in all cases but one. There was only one hospital death, the result of subpulmonic obstruction. This occurred in the first patient of this series, who had aneurysm of the membranous septum in TGA and VSD and in whom the aneurysm was not suspected preoperatively and was overlooked at surgery. There were no late deaths. In 5 patients a small residual VSD and in 3 patients a small recurrent aneurysm were found in a postoperative study. When these accompanying aneurysms are encountered during surgery or are previously diagnosed, resection or imbrication of the sac should be accomplished in order to prevent further enlargement or postoperative arrhythmias and, especially in TGA, to avoid fatal subpulmonic obstruction as occurred in our only death. According to the present data, in the presence of an aneurysm, even a small VSD should be closed by a patch and the aneurysm should perhaps be excised.


Surgical treatment of thrombosed Björk-Shiley aortic valve prosthesis. Massive thrombosis of a Björk-Shiley aortic valve prosthesis occurs with significant frequency when adequate anticoagulation has not been attained. The converse is also true: This complication is extremely rare in patients receiving anticoagulant therapy. Therefore, we recommend anticoagulants for all patients with Björk-Shiley aortic valve prostheses. Once a diagnosis of a thrombosed prothesis is made, however, immediate operation is indicated. Declotting of the valve without removal of the disc is adequate treatment. After thrombectomy, it is extremely important to evaluate the entire prosthesis critically, with particular attention to the area of the hinge and the occluder. If any wear is observed, the entire prosthesis should be replaced. Excellent long-term results can be expected if the patient is maintained on adequate anticoagulation postoperatively.


Myocardial infarction complicated by rheumatic heart disease. This report describes the case of a 32-year-old woman with the sudden onset of chest pain and an evolving inferior wall infarction proved by the electrocardiogram and enzyme studies. The patient underwent embolectomy 2 months later for a thromboembolus in the right main coronary artery. An autologous patch graft was used to close the arteriotomy. Four years later, the patient is asymptomatic, having no activity limitations. The patch graft to the right coronary artery is patent. This case exemplifies and reaffirms the possibility of emboli being lodged in the coronary arteries in certain types of disease. It may be necessary to operate in order to re-establish proper coronary circulation.


Surgical treatment of truncus arteriosus, with emphasis on infants and small children. Two of 10 children with truncus arteriosus, Type I, II, less than 2 years of age, 6 of 7 between 2 and 5 years of age, and all 5 older than 5 years survived after complete repair. Five of the nine hospital deaths are believed related to inadequate intra- and postoperative management. One late death has occurred 42 months postoperatively. The low hospital mortality rates in those 2 years of age and older, good long-term results to date, and the poor prognosis of children not operated upon indicate the advisability of elective repair at age 2 to 3 years. Although results in infants less than 2 years old have not been good, current improvements of intra- and postoperative care and the lack of a better alternative suggest that prompt primary repair is indicated for infants with intractable heart failure or increasing pulmonary vascular resistance.


Tricuspid valve prosthetic replacement. Early and late results with the Starr-Edwards prosthesis. The total experience (154 patients) with ball-valve (Starr-Edwards) replacement of the tricuspid valve, alone and in combination, through Dec. 31, 1971, at the Mayo Clinic is reviewed. The early mortality rate with isolated tricuspid replacement was twice that for tricuspid replacement combined with replacement of other valves. Among patients receiving three valves, those with "functional'' tricuspid insufficiency and those who were in New York Heart Association (N.Y.H.A.) Class IV preoperatively  had a higher early mortality rate. The early mortality rate for the total group was 28%. Of those surviving tricuspid plus mitral valve replacement, 70% were alive at 3 years; at latest follow-up, 94% of those surviving were functionally improved. Of those surviving triple valve replacement, 56% were alive at 3 years; at latest follow-up, 93% of those surviving were functionally improved. Previous cardiac surgery with residual tricuspid valve dysfunction and severe disability, as judged by N.Y.H.A. class, influenced the outcome adversely. The experience reported here provides a standard against which never prostheses can be compared.


Noninvasive diagnosis of complications of the mitral bioprosthesis. The echophonocardiographic diagnoses of valvular and paravalvular insufficiency, calcific stenosis, and thrombolic occlusion of the stent-mounted aortic homograft or heterograft in the mitral position are described. Paravalvular and valvular insufficiency were associated with apical systolic murmurs which decreased in intensity after amyl nitrite inhalation and with echocardiograms which showed initial diastolic slopes of the stents in excess of the normal range (1.9 to 3.3 cm. per second). In clinically improved and stable patients, amyl nitrite inhalation resulted in increased intensity of the commonly heard systolic ejection type murmur at the left sternal border and echocardiographic evidence of further narrowing of the outflow tract measured between the interventricular septum and the anterior portion of the stent. Calcific homograpft stenosis was associated with a decreased diastolic stent slope (0.4 cm. per second) and increased echo density from the tissue leaflets. Thrombus formation on the sewing ring caused fatal inflow occlusion in 2 patients. The condition was characterized by an echocardiogram showing decreased ratio of internal-to-external stent diameter, 0.47 (normal range 0.56 to 0.74), decreased diastolic stent slope, and decreased leaflet excursion.


Surgical treatment for closed thoracic aortic injuries. Eighteen patients with acute aortic tear secondary to nonpenetrating thoracic trauma and seven with chronic tears have been operated upon. Of the patients with acute injury, 28% had normal chest x-ray on admission. The diagnosis of acute aortic tear was made by aortography in all patients. Two patients died from causes unrelated to the aortic injury. In the group of 18 patients in which some method of perfusing the distal aorta was used, two developed paraplegia; in the group of 7 treated with simple aortic cross-clamping none occurred. The average aortic cross-clamp time 69 and 23 minutes, respectively, and average blood administration 3,139 and 1,700 ml., respectively. We conclude that the diagnosis of acute aortic tear cannot be reliably made on clinical grounds, and that with properly trained personnel the method of choice is usually simple aortic cross-clamping during repair.


Intraventricular repair of transposition complexes with ventricular septal defect. Repair of transposition of the great arteries by the technique developed by Mustard is the method routinely used for correction of such anomalies. Intraventricular repair of transposition complexes associated with a large ventricular septal defect can prevent some of the limitations and late complications of the intra-atrial operation. A technique is described of intraventricular repair of an unusual Taussig-Bing type of anomaly with a pericardial patch as a baffle to channel left ventricular outflow to the aorta and right ventricular outflow to the pulmonary artery.


Leiomyosarcoma of the pulmonary artery diagnosed preoperatively by angiocardiography. Replacement with composite graft. In a patient with rapidly progressive congestive heart failure and syncope, primary leiomyosarcoma was diagnosed by angiocardiography. The pulmonary artery was resected and replaced with a composite graft. The patient died 12 days later from myofibrillar degeneration of the right ventricle and marked pulmonary disease secondary to pre-existing bronchiectasis.


Chylothorax after median sternotomy for intrapericardial cardiac surgery. Chylothorax following cardiovascular surgery occurs with an incidence of 0.25 to 0.5 per cent. We are aware of only 5 reported cases in the literature following intrapericardial procedures. This report includes the forth documented case following ventricular septal defect closure and the first 4 reported cases following median sternotomy for intrapericardial acquired cardiac disease. The fistula in all cases occurred in the anterior mediastinum in the region of the thymic tissue. This problem can be prevented by surgical ligation of the thymic vascular structures at the time of dissection rather than the use of electrocautery. The treatment recommended is a 2 week trial of conservative therapy with a diet of medium-chain triglycerides and closed-chest suction. If this fails, surgical division of the fistula is recommended.


Synthesis and conformation of sequential polypeptides of L-alanine and beta-aminobutyric acid. Sequential polypeptides with the repeating units L-alanyl-(S)-beta-aminobutyric acid, L-alanyl-(R)-beta-aminobutyric acid, and L-alanyl-(R,S)-beta-aminobutyric acid have been synthesized by polycondensation of the N-hydroxysuccinimide ester hydrochloride salts of the corresponding dipeptides. Circular dichroism and infrared spectroscopy studies of films of the polypeptides and circular dichroism study of their solutions in hexafluoro-2-propanol and hexafluoropropane-2,2-diol show the tendency of the polypeptides to adopt the beta conformation in the solid state. In pure hexafluoro-2-propanol or hexafluoroacetone, the three polymers adopt what we interpret as random coil conformations. In mixtures of hexafluoro-2-propanol-water or hexafluoropropane-2,2-diol-water, the polypeptide containing the S isomer shows a definite tendency to form beta structure. This tendency is not established for the R and the R,S isomers.


Statistical mechanical treatment of protein conformation. I. Conformational properties of amino acids in proteins. A statistical mechanical (one-dimensional Ising model) treatment, based on the dominance of short-range interactions, is developed in this series of papers; it is intended as an improvement over empirical prediction schemes for obtaining approximate initial conformations of proteins (to be used to try to deduce the native conformation by subsequent energy minimization). In the present paper, the statistical weights for a two-state model (alpha-helical and other conformations) and for a three-state model (alpha-helical, extended, and other conformations) are evaluated from x-ray data on 16 native proteins. The method for evaluating the statistical weights is presented. Asymmetric alpha-helical nucleation parameters are also evaluated for the 20 naturally occurring amino acids. On the basis of these statistical weights, the conformational properties of the twenty naturally occurring amino acids are discussed. The statistical weights evaluated from x-ray data are also discussed in comparison with experimental results on the helix--coil transition in polyamino acids in solution. The predominant role of short-range interactions, and some possible long-range effects in determining the statistical weights, are discussed in conjunction with the mechanism of protein folding.


Statistical mechanical treatment of protein conformation. II. A three-state model for specific-sequence copolymers of amino acids. A one-dimensional three-state Ising model [involving alpha-helical (alpha), extended (epsilon), and coil (or other) (c) states] for specific-sequence copolymers of amino acids ahs been formulated in order to treat the conformational states of proteins. This model involves four parameters (wh,iota, vh, iota, v episilon, iota, and uc, iota), and requires a 4 X 4 matrix for generating statistical weights. Some problems in applying this model to a specific-sequence copolymer of amino acids are discussed. A nearest-neighbor approximation for treating this three-state model is also formulated; it requires a 3 X 3 matrix, in which the same four parameters appear, but (as with the 4 X 4 matrix treatment) only three parameters (wh, uh, and v epsilon) are required if relative statistical weights are used. The relationship between the present three-state model (3 X 3 matrix treatment) and models of the helix--coil transition is discussed. Then, the three-state model (3 X 3 matrix treatment) is incorporated into an earlier (Tanaka--Scheraga) model of the helix-coil transition, in which asymmetric nucleation of helical sequences is taken into account. A method for calculating molecular averages and conformational-sequence probabilities, P(iota/eta/(rho)), i.e., the probability of finding a sequence of eta residues in a specific conformational state (rho), starting at the iotath position of the chain, is described. Two alternative methods for calculating P(iota/eta/(rho)), that can be applied to a model involving any number of states, are proposed and presented; one is the direct matrix-multiplication method, and the other uses a first-order a priori probability and a conditional probability. In this paper, these calculations are performed with the nearest-neighbor model, and without the feature of asymmetric nucleation. Finally, it is indicated how the three-state model and the methods for computing P(iota/eta/(rho)) can be applied to predict protein conformation.


Comments on exclusion of polymer chains from small pores and its relation to gel permeation chromatography. Some criticisms of our theoretical treatment of the partial exclusion of flexible-chain polymers in solution from cavities of macromolecular size and its application to gel permeation chromatography are examined. In other discussion, it is confirmed by simple reasoning that the identification, explicit or implicit in various studies, of the mean projection of a polymer molecule onto a line as a characteristic dimension governing the extent of permeation of simple pores does not depend on specific molecular models. Our previous calculation of permeation by certain random-flight branched-chain species is shown to lead, incidentally, to the mean projection for these structures. From relations between the mean projection and the hydrodynamic volume of a molecule, it appears that the product of intrinsic viscosity and molecular weight is not a common calibration factor for elution of all molecular species from a gel chromatographic column, but theory and experience do support the validity of this correlation among solutes with similar molecular architecture.


Statistical mechanical treatment of protein conformation. III. Prediction of protein conformation based on a three-state model. The method proposed for the evaluation of statistical weights in paper I, and the three-state model [alpha-helical (alpha), extended (epsilon), and other (c) states] formulated in paper II, have been used to develop a procedure to predict the backbone conformations of proteins, based on the concept of the predominant role played by shortrange interactions in determining protein conformation. Conformational probability profiles, in which the probabilities of formation of three consecutive alpha-helical conformations (triad) and of four consecutive extended conformations (tetrad) have been defined relative to their average values over the whole molecule, are calculated for 19 proteins, of which 16 had been used in paper I to evaluate the set of statistical weights of the 20 naturally occurring amino acids. By comparing these conformational probability profiles to experimental x-ray observations, the following results have been obtained: 80% of the alpha-helical regions and 72% of the extended conformational regions have been predicted correctly for the 19 proteins. The percentage of residues predicted correctly is in the range of 53 to 90% for the alpha-helical conformation and in the range of 63 to 88% for the extended conformation for the 19 proteins in the two-state models [alpha-helical (alpha) and other (c) states, and extended (epsilon) and other (c) states]. In the three-state model, the percentage of residues predicted correctly is in the range of 47% to 77 for 19 proteins. These results suggest that the assumption of the dominance of short-range interactions, on which the predictive scheme is based, is a reasonable one. The present predictive method is compared with that of other authors.


Further echocardiographic observations in pericardial effusion. Although the presence of fluid behind the left atrium, on echocardiography, has been used to differentiate pleural from pericardial effusions, five cases are reported showing that pericardial fluid can and does accumulate behind the left atrium. Abnormal valvular motion, as a result of free swinging of the heart in the pericardial sac, was also demonstrated in these patients.


Helix--coil stability constants for the naturally occurring amino acids in water. X. Tyrosine parameters from random poly(hydroxypropylglutamine-co-L-tyrosine). The synthesis and characterization of water-soluble random copolymers containing L-tyrosine with N2-(3-hydroxypropyl)-L-glutamine are described, and the thermally induced helix--coil transitions of these copolymers in water have been studied. The incorporation of L-tyrosine was found to increase the helix content of the polymers at all temperatures. The Zimm-Bragg parameters sigma and sigma for the helix--coil transition in poly(L-tyrosine) in water were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The large value of sigma indicates that, in water, tyrosine has a tendency to promote helix--coil boundaries at all temperatures; the values of sigma indicate that this residue enhances helix growth at low temperature and reduces it at high temperature.


Moments and distribution functions for polypeptide chains. Poly-L-alanine. Statistical mechanical averages of vectors and tensors characterizing the configurations of polypeptides have been calculated for poly-L-alanines (PLA) of xu = 2-400 peptide units. These quantities are expressed in the reference frame of the first peptide unit, the X axis being situated along the virtual bond, the Y axis in the plane of the peptide unit. The persistence vector a identical to (r) converges rapidly with chain length to its limit a infinity which lies virtually in the XZ plane. Configurational averages of Cartesian tensors up to the sixth rank formed from the displacement vector p = r-a have been computed. For xu greater than 50 the even moments of fourth and sixth rank formed from the reduced vector p for the real chain are well repreented by the freely jointed chain with 21.7 virtual bonds equivalent to one of the model. The moments of p display assymmetry for xu less than 50. Density distribution functions Wa(p), evaluated from the three-dimensional Hermite series truncated at the term in the polynomial involving the tensors of p of sixth rank, display no obvious symmetry for xu less than 50. Approximate spherical symmetry of the distribution of p about a is observed only for xu greater than or equal to 100.


Elevated plasma antidiuretic hormone levels in status asthmaticus. Elevated plasma antidiuretic hormone (ADH) levels were noted in seven patients with status asthmaticus during the acute illness. These values returned to normal with resolution of the disease. The mechanism of this release is not completely understood but is consistent with the hypothesis that bronchospasm leads to decreased pulmonary blood flow, decreased volume return to the left atrium, and stimulation of the atrial volume receptors regulating ADH release. Planning for fluid therapy in patients with status asthmaticus should take into account a high probability of increased plasma ADH concentration during the acute illness. Water intoxication as well as hypoxia and hypercarbia should be considered as a possible cause of an altered state of consciousness associated with status asthmaticus.


Conformation of cyclo-(L-Leu-L-Tyr-delta-Avaler-delta-Avaler), a synthetic inhibitor of chymotrypsin, by x-ray analysis. The synthetic cyclic tetrapeptide (L-Leu-L-Tyr-delta-Avaler-delta-Avaler) is an effective inhibitor of chymotrypsin, competitive with linear peptides like Ac-L-Leu-L-Tyr-OMe. An x-ray diffraction analysis of the crystal structure of the cyclic peptide shows that the conformation of the 18-membered ring is very similar to that of one of the four conformers of cyclic hexaglycyl. There is no internal hydrogen bonding. Side chains are located on two "corners" of the approximately rectangular ring. The chii1 angles for Leu and Tyr are -74 and -48 degrees, respectively. The Leu side chain is extended away from the polypeptide ring while the Tyr side chain is folded under an adjacent carbonyl bond. The cell parameters for the space group P2U are: a = 9.361 (3 A, b = 19.039 (10) A, c = 9.603 (3), A, and beta = 116.54 (3) degrees. A molecule of (CH3)2SO (disordered) and a molecule of H2O cocrystallized with the cyclic peptide.


Fine structural morphometry of diffuse lung diseases with abnormal blood-air gas transfer. Samples of lung biopsy tissue from nine patients with normal lungs, seven with pulmonary sarcoidosis, nine with diffuse interstitial pulmonary fibrosis, seven with histiocytosis X, and one with asbestosis were analyzed by morphometric techniques applied to electron micrographs, and the results were subjected to rank-sum analysis. Within the limits of the sampling method and the mathematical predictions of others, the general rejection of the constructed hypothesis in this study supports the conclusion that factors other than increase in the arithmetic of harmonic mean thickness of the blood-air barrier are critical to impaired gas transfer in the diseases studied.


An aflatoxin in the liver of a patient with Reye-Johnson syndrome. Liver specimens from 8 patients with Reye-Johnson syndrome, 2 patients with acute encephalopathy, and 10 patients without liver disease were analyzed for aflatoxins. An aflatoxin was obtained from the liver of one patient, a 15-year-old girl who had clinical, laboratory, and pathologic features of Reye-Johnson syndrome. Thin-layer chromatography, fluorescence emission, infrared spectroscopy, and derivatization studies characterized the aflatoxin as related structurally to but not identical with aflatoxin B1. This report is added to previous ones from Thailand, New Zealand, and Czechoslovakia in which the association of aflatoxins and fatty liver has been found in Reye-Johnson syndrome.


Frictional properties of dilute block-copolymer solutions and homopolymer solutions. Application to molecular weight determination. An equation for the translational diffusion coefficient of block copolymers in dilute solution has been obtained by modifying Zimm's equation for homopolymers to take into account the existence of dissimilar segments in block copolymers. Illustrative calculations for homopolymers and block copolymers have been made and the results for homopolymers have been compared with experiments and with the calculations of Yamakawa and Fujii. A procedure has been proposed to determine the molecular weight of a block copolymer from measurements of its limiting viscosity number and its sedimentation coefficient or translational diffusion coefficient.


The epidemiology of primary intracranial neoplasms of childhood. A population study. All primary intracranial neoplasms diagnosed between 1935 and 1964, inclusive, in the well-defined populations of children under age 15 residing in the state of Connecticut and the city of Rochester, Minnesota, formed the basis for this study. The tumors occurring in this group were characterized by histologic type and by the patient's sex and the age when the tumor occurred. In Connecticut, over the 30-year period, a primary intracranial neoplasm was diagnosed in 380 patients in a mean population of 582,286 children, yielding an average annual incidence rate of 2.17 cases/100,000 population per year. Of the microscopically confirmed tumors, the most common, in order, were medulloblastoma (24.2%), astrocytoma (20.6%), glioblastoma (20.3%), ependymoma (6.5%), craniopharyngioma (5.6%) and meningioma (4.6%). These figures contrast sharply with the corresponding frequency of these tumors in the adult Connecticut population. In Rochester during the same years, 12 primary intracranial neoplasms occurred in a mean population of 7,981 children, yielding an average annual incidence rate of 5.01 cases/100,000 population per year.


Ricinoleic acid (castor oil) alters intestinal surface structure. A scanning electronmiscroscopic study. To determine if sodium ricinoleate, the active principle of castor oil, alters mucosal surface structure of the small intestine, rabbit ileum was perfused with isotonic buffer or buffer containing 10 mM of sodium ricinoleate. Mucosal biopsies were examined by scanning electron microscopy. Sodium ricinoleate produced deep clefts or holes at the tips of villi, and at the bases of these clefts unusual cells could be resolved. The microvillus surface of the intestine was also altered at the tips and sides of villi. Microvilli were clumped into "tufts" with numerous intervening "cracks" appearing on the surface. These changes may relate to the well-documented capacity of ricinoleate and dietary long-chain fatty acids to evoke fluid secretion in the intestine. The findings thus pertain to the pharmacology of castor oil and the pathophysiology of steatorrheal disease.


[Experimental and clinical investigations in pathophysiology of renal artery stenosis (author's transl)]. The effect of renal artery stenosis on the poststenotic hemodynamics is demonstrated and evaluated in the presented experimental and clinical investigation. It is shown that the resistance of a medium sized stenosis is small compared to the total renal resistance. The peripheral resistance which is induced by the stenosis is the essential characteristic in the pathophysiology of the renal artery stenosis and the resulting hypertension. The increasing pressure can be measured primarily in the stenosed artery and later also in the not stenosed side and is seen as an effect of the renin-angiotensin-mechanism. The renal artery flow returns to normal after removal of the experimental stenosis. Likewise the reduction in renal artery flow is normalized by resection of the stenosis in the initial phase of the clinical renal artery stenosis. The induced hypertension is reversed to normal. Since the resistance in the initial phase is essentially limited to the stenosed side the global renal resistance is only little increased. Increased total renal resistance is due to morphological changes in the peripheral vessels. The removal of the stenosis will not be followed by a decrease in bloodpressure. This is to be seen in the data of our clinical cases. The critical limit for an effective operation followed by a decrease in artery pressure is to be seen in a total renal resistance of over 0.25 mm Hg/ml min-1.


[Histological findings after transabdominal ligation-resection of the esophagus ad modum boerema (author's transl)]. The esophagus was histologically studied in ten patients, who died after transabdominal ligation-resection of the esophagus ad modum Boerema because of bleeding esophageal varices. The patients had survived the operation for various periods of time. The questioning was, if with this operation with a higher incidence of parietal leakage following mediastinitis and peritonitis has to be calculated. We could not confirm that hypothesis. On the contrary we recognized at the level of the ligation simulataneously degenerated muscles fibres and a regeneration of the esophageal wall by fibrous tissue compensation.


[Duodenogastric reflux after vagotomy and pyloroplasty (author's transl)]. In 27 patients after selective or truncal vagotomy and pyloroplasty the occurrence of duodenogastric reflux was checked by two methods, by the measurement of Bromsulphalein (BSP)-concentration in the gastric aspirate after BSP was given intravenously and by instillation of a barium meal in the second part of the duodenum followed by upper GI-series. In 20 of 23 patients reflux was recorded radiologically, in 18 of 27 patients reflux was shown by the BSP-Method. Proven bile reflux was associated with major postoperative discomfort, such as epigastric fullness, nausea and epigastric pain, it was also associated with gastritis as shown by microscopic examination of biopsies taken from the antrum. It is recommended to consider duodenogastric reflux as a possible reason for patients complaints after vagotomy and pyloroplasty. To avoid those complaints the preference of proximal gastric vagotomy without pyloroplasty is supported, if preoperative gastric emptying is not impaired.


[Clinical results by selective proximal vagotomy with pyloroplasty (author's transl)]. The results of selective proximal vagotomy and pyloroplasty for duodenal and gastric ulcer in 464 patients over the last 5 years were evaluated in 438 cases. More than 75% of the patients were observed for 2 years after the operation. More than 25% were emergency cases, the incidence of intraoperative complications like splenic lesions or perforation of the esophagus was 3.2%. Postoperative complications like leakage of the pyloroplasty, peritonitis, hemorrhage from the pyloroplasty or disruption of the laparotomy closure occurred in 14,4%. The overall mortality was 4.6%, the elective mortality 1.6%. Recurrent ulcers were seen after 1/2-2 1/4 years with an overall rate of 3.2%. Over half of these cases required relaparotomy. In 5.3% relaparotomy had to be done for peritonitis, GI-bleeding, bleeding from the lesser curvature of the stomach, ileus or carcinoma. The Pentagastrin stimulated gastric secretion remained constantly reduced for more then 2 years in over 60%. Following the Visick-grading system the results were good in 61-65% of the patients and bad in 16-22% depending on the time of observation.


[Blood supply and histophysiology of the appendices epiploicae (author's transl)]. The appendices epiploicae of the colon wall are constituted of three morphologically different types: stalked appendices and others which are attached with their base in longitudinal and vertical direction to the colon axis. The appendices have a characteristic blood supply which varies with the different forms. In difference to other regions of the fat-organ in the human body an increased number of interstitial cells between capillaries and fat-cells can be found. These cells are obviously inserted in the insulin-controlled fat metabolism of the appendices. The interpretation of these morphological findings is that functionally the appendices may play a role in the resorption of water and electrolytes from the colon contents.


[Embolism by ultrasound-thrombolysis (author's transl)]. By ultrasound it is possible to destroy thrombi intravascular and remove them by a hollow flexible probe at the same time. Experiments were now performed in 6 dogs with 2-9 days old thromboses in the femoral or iliac veins, to detect embolisation during ultrasound-thrombolysis. Parameters were pulmonary angiograms and lung scans. Only in one dog with a floating thrombus in the iliac vein signs of pulmonary embolism were found after thrombolysis. The controls of the other 5 dogs were normal.


[Aortic arch syndrome (author's transl)]. This report demonstrates a case of a fully developed aortic arch syndrome with an unusual lack of symptoms. A sufficient collateralisation and nearly free cerebral vessels were hiding the clinical manifestations of arteriosclerosis for a long time. Besides the diagnostic maneuvers the operative therapy is shown during which a short, acute circulatory failure occurred caused by a reflex reaction of the carotic sinus due to the improved blood supply.


[Postoperative changes in immunoglobulin-concentrations after splenectomy. A prospective survey series (author's transl)]. The three immunoglobulin classes A, G and M were quantitatively determined through immune diffusion preoperatively as well as in the first 60 days in 31 patients after splenectomy and the results were statistically evaluated. In comparison with the initial preoperative values, a temporary, significant elevation of the serum concentration of the IgA and IgG was found, whereby the IgA concentration on the 60th postoperative day corresponded already to the preoperative initial values, whilst the IgG were at this time still significantly elevated. There was a beginning significant decrease in serum concentration of the IgM between the 15th and 20th postoperative day, which was very pronounced on the 60th day. This determination coincides with the half-life time of the IgM and can be regarded as an indication for a localisation of the IgM producing cells in the spleen.


[Preoperative analysis of the gastric secretion as guidance for the operative procedure of peptic jejunal ulcers (author's transl)]. The development of a peptic jejunal ulcer after partial gastrectomy may result either from a technical deficiency of the anastomotic region, a seldom-occurring gastrin producing tumor, a displacement of the pyloric antrum into the alkaline milieu of the duodenal stump, an abnormally high vagus tone, or from too low a resection. In 17 out of 32 patients with a peptic jejunal ulcer preoperative gastric secretion analysis were performed during consecutive stimulation of the gastric secretion by gastrin-pentapeptide, histalog, and insulin-induced hypoglycemia. A high basal secretion, which could only be minimally stimulated by exogenous gastrin, required the operative revision of the duodenal stump. A vagotomy was found to be sufficient in patients reacting strongly to hypoglycemia and moderately to gastrin-pentapeptide or histalog. A hypersecretion after stimulation by gastrin-pentapeptide, histalog as well as by hypoglycemia was an indication for a re-resection of the gastric stump. The latter was combined with vagotomy if both the basal and the stimulated secretion values were found to be increased to higher levels. Up to now the postoperative conditions of the patients seem to give support to the procedure applied. It should be possible to reduce the operative letality of the re-resection of peptic jejunal ulcers on the basis of the aforementioned careful selection. Out of the 32 patients of this study only one was lost.


Phospholipid exchange proteins in rat intestine. The 105,000 g supernatant and pH 5.1 supernatant fractions from rat intestinal homogenates stimulate phosphatidylcholine exchange between [32P] phosphatidylcholine liposomes and beef heart mitochondria. This active fraction shows the characteristics of a protein. Isoelectric focusing of the intestinal pH 5.1 fraction shows two peaks of phosphatidylcholine exchange activity: one at an acidic pH (4.5-5.3), the other in a basic pH range (8-9). The second peak of activity appears to be a new phospholipid exchange protein. The anatomic distribution of phosphatidylcholine exchange activity in intestine has been investigated. Expressed per mg of protein, phosphatidylcholine exchange activity is higher in mucosa than in the intestinal wall. No significant differences have been found between villi and crypts cells or between jejunal and ileal villi. Futhermore, exchange activity per mg of protein in mucosa is unaffected by fasting or by feeding a high fat or high cholesterol diet. This suggests that phospholipid exchange activity in the absorptive cells is not a rate limiting step in the process of fat absorption.


Neutral lipid composition of Culex quinquefasciatus and Culex tritaeniorhynchus cells at two phases of growth. The mosquito cells Culex quinquefasciatus and Culex tritaeniorhynchus were grown in spinner cultures. The fatty acid profiles of the neutral lipid classes were analyzed, and comparisons were made between the two species at logarithmic and stationary phases of growth and between the species and the medium. The results from the data suggest an increase in the average chain length of the fatty acids in the free fatty acid and sterol ester fractions of the Culex quinquefasciatus cells with aging. From the logarighmic to stationary phase, both Culex cells showed some increase in desaturation of acids in the di- and triglyceride and free fatty acid fractions. The Culex tritaeniorhynchus cells also showed some increase in desaturation of acids in the monoglyceride fraction. Differences between the two Culex species at the logarithmic phase of growth were observed in the fatty acid profiles of all the neutral lipid fractions examined and at the stationary phase of growth in the free fatty acid, triglyceride, and sterol ester fractions.


Comparison of the lipid composition of Culex quinquefasciatus and Culex tritaeniorhynchus cells obtained from the logarithmic and stationary phases of growth. Culex quinquefasciatus and Culex tritaeniorhynchus cells were grown in spinner culture medium. The cells were harvested at late logarithmic and stationary phases of growth. The total lipid, total neutral lipid, and total phospholipid contents of the cells were analyzed to determine changes that occurred in the fatty acid profiles of the lipids with aging and between species. There was an increase in the amount of total neutral lipids with a corresponding decrease in amount of total phospholipid from logarithmic to stationary phases of growth of the Culex quinquefasciatus cells. Chain elongation and/or desaturation of acids occurred with aging of cells. The fatty acids of the phospholipids had a longer average chain length than the neutral lipids.


Effect of dietary fat supplementation on the composition and positional distribution of fatty acids in ruminant and porcine glycerides. Dietary fats which were protected from ruminal metabolism were fed to ruminants, and the constituent fatty acids subsequently appeared in the glycerides of tissues and secretory products. These dietary fat induced alterations in tissue lipid composition were particularly apparent when the fat source was enriched with linoleic acid. Similarly, when pigs were fed linoleic-enriched fats, the linoleic acid was incorporated into the adipose tissue triglycerides. Stereospecific analyses were carried out on triglycerides from various tissues and secretory products obtained from animals fed control or linoleate-enriched diets. The analysis of adipose tissue triglycerides showed that linoleate and oleate were preferentially esterified to positions 2 and 3 (cattle and sheep), and positions 1 and 3 (pigs). Of the other major adipose tissue fatty acids, palmitate was preferentially esterified at position 1  (ruminants) and position 2 (pigs), and stearate was preferentially esterified at positions 1 and 3 (ruminants), and position 1 (pigs). Stereospecific analysis of high mol wt milk triglycerides showed that linoleate was either evenly distributed on all three positions (goats), or predominantly on position 3 (cows). Furthermore, the incorporation of this linoleate did not markedly alter the positional specificity of the other major milk triglyceride fatty acids. Of these fatty acids, the short and medium chain length acids (butyratelaurate) were mainly on position 3, myristate and palmitate on positions 1 and 2, and stearate and oleate evenly distributed. Thoracic duct lymph triglycerides from sheep tended to show preferential incorporation of linoleate at position 3, palmitate at position 2, and stearate at position 1 and 3; oleate, on the other hand, tended to be evenly distributed on all three positions of the lymph triglyceride. The stereospecific arrangement of fatty acids in sheep liver triglycerides was similar to that of lymph triglycerides, and this may reflect the uptake of intact or partially hydrolysed chylomicron and/or very low density lipoprotein triglycerides by the liver. There were also some analogies in the stereospecific arrangement of fatty acids on ruminant lymph and milk triglycerides and this may reflect an incomplete hydrolysis of chylomicron and/or very low density lipoprotein triglycerides prior to uptake by the mammary gland. An unusual feature of lymph from sheep fed linoleate was the presence of phospholipids which contained large amounts of linoleate in ca.  equal proportion at both positions 1 and 2 of the phospholipid molecule.


Effect of cold stress on rapeseed oil fed rats. No mortality was observed in 6 week old male Sprague-Dawley rats subjected to cold at 4 C for 3 weeks and fed either a control diet (Chow) or a semisynthetic diet containing 20% by wt rapeseed oil high in erucic acid (23.6%). All rats fed the Chow diet and 17 of 20 rats fed the rapeseed oil-containing diet survived 4 weeks in the same environment. Three rats on the latter diet died of self-mutilation. Marked myocardial lipidosis as well as a large acumulation of 20:1 and 22:1 was observed in the hearts of rats fed the rapeseed oil-containing diet. Five of 20 rats on the Chow diet and 2 of 20 rats on the rapeseed oil-containing diet had focal necrotic areas in the myocardium.


Turnover of fatty acids in rat liver cardiolipin: comparison with other mitochondrial phospholipids. Following intraperitoneal administration of 1-14C-linoleic acid or 2-3H-acetate to rats, the specific radioactivities of both liver cardiolipin and other mitochondrial phospholipids after different time intervals were measured. Comparison of the data obtained with those from another stock of rats treated with 32P-phosphate or 2-3H-glycerol showed that the fatty acids of cardiolipin, like those of other phospholipids, exhibit an independent turnover with respect to the remaining parts of the molecule. The half-life of acyl moieties of cardiolipin is ca. 20% higher than that of the same components of other mitochondrial phospholipids. Moreover, it appears that, in both cardiolipin and other phospholipids, linoleyl residues turn over faster than nonessential fatty acids. Discussion is made as to whether this characteristic can be related to the role of phospholipids in the functioning of some enzymes bound to the inner mitochondrial membrane.


Biosynthesis of polyunsaturated fatty acids in the developing brain: I. Metabolic transformations of intracranially administered 1-14C linolenic acid. Thirteen-day old rats were given intracranial injections of 1-14C linolenic acid (all cis 9, 12, 15 octadecatrienoic acid) and were sacrificed after 8 hr. Analysis of brain fatty acids showed that 16:0, 18:0, 18:1, 18:3, 20:3, 20:4, 20:5, 22:5, and 22:6 were labeled. The total fatty acid methyl esters were separated into classes according to degree of unsaturation on a AgNO3:SiO2 impregnated plate. The bands were scraped off and the eluted fatty acids were first analyzed by radio-gas liquid chromatography and then subjected to reductive ozonolysis to determine double bond position. The saturated acids, 16:0 and 18:0, as well as the monosaturated 18:1, must have been formed from radioactive acetate produced by beta oxidation of the injected linolenate. Among the polyunsaturated fatty acids, the triene fraction was characterized and identified as 18:3 omega3 (delta9, 12, 15), the starting material, and 20:3 omega3 (delta11, 14, 17); the tetraene fraction was identified as 20:4 omega3 (delta2, 11, 14, 17); the pentaene fraction was identified as 20:5 omega3 (delta5, 8, 11, 14, 17) and 22:5 omega3 (delta7, 10, 13, 16, 19); and, finally, the hexaene fraction was shown to be 22:6 omega3 (delta4, 7, 10, 13, 16, 19). The biosynthesis of these omega3 family fatty acids in the brain in situ is discussed.


Monocarboxylic acids from oxidation of acyclic isoprenoid alkanes by Mycobacterium fortuitum. Mycobacterium fortuitum utilizes certain stereoisometric mixtures of individual multimethyl branched alkanes as sole carbon source, including 2,6(R), 10(S), 14(RS)-tetramethylhexadecane; 2.6(R), 10(S), 14(RS)-tetramethylheptadecane; 2,6(RS), 10(RS)-trimethyltetradecane, and 2,6(R), 10(S)-trimethylpentadecane. Products of oxidation isolated from the bacterial lipids were acids derived predominantly from oxidation of the isopropyl terminus of each alkane, except in the case of 2,6(RS), 10(RS)-trimethyltetradecane. With the latter, acids from oxidation at either terminus were detected in comparable proportions.


Cuticular lipids of insects: VIII. Alkanes of the Mormon cricket Anabrus simplex. The cuticular hydrocarbons of the Mormon cricket, Anabrus simplex, are all saturated and consist of n-alkanes (29+%), 3-methylalkanes (12%), internally branched monomethylalkanes (26+%), and dimethylalkanes (28+%). The principal n-alkane is the C29 component, with a range from C23 to C33. The 3-methylalkanes range from C28 to C32, and the internally branched monomethyl- and dimethylalkanes range from C29 to C39. When the branched alkanes of A. simplex are compared to those from other insects in the order Orthoptera, interesting patterns of methyl branching are observed.


In vitro activity of the fatty acyl desaturases of human cancerous and noncancerous tissues. The microsomal desaturase activity of human cancerous and noncancerous tissues was measured in vitro using 1-14C, -11, 14-eicosadienoic and 1-14C-oliec acids as substrates. Tissues used were a case of ovarian cancer, a urinary bladder cancer, a rectal cancer, and a non-specific colonic ulcer with appropriately normal tissues. When 11, 14-20:2 was used as substrate, radioactive tetraene and triene were produced. The tetraene was identified by radio gas chromatography as arachidonic acid (5, 8, 11, 14-20:4), and the triene had a retention time of 5, 11, 14-20:3. Thus, the possibility arises that a delta8 desaturase was involved. In the delta6 desaturase, with the urinary bladder cancerous tissue, the desaturase activity appeared to be decreased in comparison to neighboring tissue, whereas with the colonic cancer tissue, the desaturase appeared to be relatively increased, though the number of samples was inadequate for confidence.


Relationship between erucic acid and myocardial changes in male rats. The back and belly fat of pigs fed a diet containing 20% by wt rapeseed oil (22% erucic acid) for 16 weeks was rendered into oil. This rendered pig fat, which contained 5.6% erucic acid, was fed to male rats in three separate experiments at 20% by wt of the diet for 16 weeks. In experiment I rendered pig fat was compared only to Brassica campestris var. Span rapeseed oil containing 4.8% erucic acid. In experiments II and III, rendered pig fat was compared to commercial lard containing 0.2% docosenoic acid, commercial lard to which 5.4% free erucic acid was added, and Span rapeseed oil. There was no significant (P less than 0.01) differences observed in the level of erucic acid in the hearts of rats fed diets of rendered pig fat, Span rapeseed oil, or commercial lard plus erucic acid. However, the incidence (P less than 0.001) and severity (P less than 0.01) of cardiac lesions were significantly higher in Span rapeseed oil fed rats compared to rats fed control diets. The number of rats affected or the severity of lesions in the rendered pig fat fed group was not significantly different from controls. The results of this study indicate that the myocardial lesions associated with feeding 20% rapeseed oil diets are not related to the content of erucic acid per se. The possible reasons why rapeseed oil causes cardiac lesions in rats are discussed. It is suggested that a triglyceride imbalance in the oil might play an important role in causing these lesions in rats.


Addition of N-acetylcysteine to linoleic acid hydroperoxide. Catalyzed by 10(-5)M ionic iron in 80% ethanol, N-acetylcysteine added to linoleic acid hydroperoxide, forming a thiobond. Reaction of a specific isomer of hydroperoxide, 13-hydroperoxy-trans-11, cis-9-octadecadienoic acid, and N-acetylcysteine, forms a number of products, of which two were identified as addition compounds. One addition product was 9-S-(N-acetylcysteine)-13-hydroxy-10-ethoxy-trans-11-octadecenoic acid, and the other was 9-S-(N-acetylcysteine)-10, 13-dihydroxy-trans-11-octadecenoic acid.


Dual-labeled technique for human lipid metabolism studies using deuterated fatty acid isomers. Two deuterated fatty acids, elaidated2 and oleate-d4, were fed simultaneously to a human subject as a mixture of trielaidin-d6 and triolein-d12. Periodically, blood samples were drawn, and red blood cells were separated from the plasma. Red blood cells and plasma lipids were fractionated and analyzed by combined gas chromatography--multiple ion mass spectroscopy. Dual deuterium-labeling allows rate and extent of fatty acid incorporation to be followed in various plasma and red cell neutral and phospholipid fractions. Maximum amount of deuterated fat varied from 4% in cholescurred in either 6-, 8-, or 12-hr samples; generally, less than 1% labeled fatty acids could be detected in 72-hr samples. Because the method is based on dual-labeling, differences in the relative incorporation of both fatty acid isomers can be compared directly. Differences in rates of incorporation, rates of removal, and extent of incorporation of labeled fatty acids into blood plasma can also be determined reliably. Our experimental labeling of fats with deuterium permits for the first time the metabolism of two fatty acid isomers to be compared simultaneously in human subjects. This new method should be applicable to a variety of other lipid metabolic studies.


Effect of eicosa-5, 8, 11, 14-tetraynoic acid on fatty acid composition of selected organs in the rat. Eicosa-5, 8, 11, 14-tetraynoic acid or archidonic acid or no supplement (controls) was given orally to rats maintained on a fat free diet and the fatty acid composition of total lipids of several organs determined. No changes were noted in the total fatty acid concentrations of the organs examined in the various groups. A decrease in the amount of arachidonic acid, 22:4omega6 and 22:5omega 6 (as percent of total fatty acids), and an increase in the amount of 20:3omega6 and linoleate were observed in total lipids of several organs. In the group receiving the arachidonate supplement, there was less linoleate and 20:3omega 6 and more archidonate than in the controls. Both eicosa-5, 8, 11, 14-tetraynoic acid and arachidonate supplements resulted in a decrease in 20:3omega9 in most organs studied. Generally, the most marked changes were seen in liver but, of the other organs examined (heart, kidney, testis, brain, and adrenals), only the adrenals failed to show any significant differences between the controls and each of the two supplemented groups. Although the experimental conditions preclude conclusive interpretation of the changes observed, it is suggested that eicosa-5, 8, 11, 14-tetraynoic acid was effective in inhibiting the conversion of linoleate to archidonate and the conversion of arachidonate to 22:4 and 22:5.


Variations in lipid composition and sound velocity in melon from the North Atlantic Pilot whale, globicephala melaena melaena. Nonpolar lipids and sound velocity at different distances from the skin surface within a sample of pilot whale melon were studied. Thin layer chromatography, sensitive radioisotopic methods, and an ultrasonic echo scanner were used. Wax esters had a maximum concentration at 11-12 cm from the skin surface. Non- and monoisovalero triglycerides both exhibited a minimum at 8-10 cm, whereas the diisovalero species increased steadily from the skin surface towards the center of the pilot whale head. A minimum of sound velocity, ca. 1340 m/s, was found at 9-11 cm, thus coinciding with a region rich in isovaleric acid esterified in wax and diisovalero triglycerides. These findings are compatible with predictions based on the known correlations between lipid structure and sound velocity. Consequently, additional evidence for refraction of sound in pilot whale melon is presented. This is important in understanding the system of echolocation of toothed whales.


Effect of transplanted human ovarian cancer tissue on liver lipid metabolism of nude mice. The changes in the lipids of liver tissues of nude mice with and without transplanted human cancerous tissues were studied to clarify the effect of transplanted human tumor tissues on host liver lipid metabolism. The total lipid was extracted and separated into phospholipid, triglyceride, and other fractions by thin layer chromatography. The amounts of methyl esters of fatty acids of each lipid fraction were measured by quantitative gas liquid chromatography after each lipid fraction had been subjected to methanolysis by 5% HC1-methanol. The phospholipid content of liver tissues of six tumor bearing nude mice was increased and the triglyceride content decreased in comparison with these fractions in three control nude mice. The ratio of the phosholipid fatty acid content to the triglyceride fatty acid content (phospholipid:triglyceride[PL:TG]) of six tumor bearing nude mice was distributed between 7.6 and 33.5, whereas PL:TG ratios of three control nude mice were distributed between 1.7 and 3.8. This result was similar to that reported for human liver tissues of patients with malignant neoplastic disease, indicating that nude mice with transplanted human cancer may be useful for clarifying the mechanisms of the lipid-chemical changes of liver tissues of patients with malignancies.


Bile acid pool in Wistar rats.

Bile acid pool in Wistar rats. The bile acid pool was found to be ca. 50 mumoles/100 g body wt in male and female rats maintained on standard laboratory chow and ca. 30 mumoles/100 g body wt in those maintained on a standard semisynthetic diet. The distribution of bile acids within the pool was similar in plasma, liver, and intestinal tract, except for a higher concentration of deoxycholic acid in the intestinal tract. Sex differences in bile acid composition were found to be influenced by the dietary regimen of the animals.


Influence of prostaglandins on plasma glucagon levels in the rat. The effect of PGE1and PGA1 intravenous infusion (2/mug/min) on plasma glucose and glucagon levels was investigated in normal, sympathectomized and propranolol-treated rats. PGE1 infusion significantly increased glucose and glucagon levels, while PGA1 had no effect. Since the dose of PGE1 used in this study was able to reduce the arterial blood pressure by about 20%, the possibility that PGE1 acted indirectly through a reflex sympathetic overactivity was tested. The increases in plasma glucagon induced by PGE1 occurred also in sympathectomized or in beta-blocked animals. Thus, it was possible to exclude a sympathetic mediation or a direct stimulation of pancreatic beta-receptors as a likely mechanism of PGE1 action.


Histamine-induced hypocalcemia in the rat. The effect of histamine and betazole hydrochloride (Histalog) on serum calcium homeostasis in the rat was studied in these experiments. Either histamine base, histamine phosphate, betazole, or the appropriate control solution was injected intravenously into fasted, anesthetized 80-100 g male rats. Venous blood was collected before and at 30 and 60 min postinjection. Histamine base in doses of 0.5-2.0 mg/rat induced a significant hypocalcemic response 30 min postinjection which returned to baseline by 60 min. Likewise, the administration of 1.375 mg/rat of histamine phosphate (equivalent to 0.5 mg histamine base) also resulted in a significant fall in serum calcium concentration. However, betazole administration, in doses as high as 10 mg/rat, did not lower the serum calcium concentration. In the histamine experiments neither total protein nor hematocrit values differed from control at the time of hypocalcemia. Therefore the changes in serum calcium concentration cannot be explained by hemodilution. These experiments demonstrate that in the rat the administration of histamine results in a hypocalcemic response similar to that previously observed with gastrin.


Parathyroid activity and bone formation. Patients of both sexes with primary hyperparathyroidism showed increments in the total subperiosteal diameter and the medullary cavity diameter of the second metacarpal bone. When two groups of females of similar age were compared, those with hyperparathyroidism had significantly greater total metacarpal area and medullary area than that of hypoparathyroid patients. An increased subperiosteal apposition has therefore been found in primary hyperparathyroidism. This might be due to a direct stimulation of PTH on bone formation at the subperiosteal surface or to a nonspecific compensatory response to endosteal resorption.


Heparin metabolism and heparin-release lipase activity during long-term estrogen-progestin treatment. Short-term oral contraceptive therapy has been reported to decrease postheparin lipolytic activity (PHLA). Resistance to heparin has been held responsible for this effect. To test several alternative explanations, we studied both PHLA and heparin concentrations in nine control women and nine women receiving long-term estrogen-progestin therapy after they were given heparin intravenously (10 units/kg). There were no significant differences in the concentration of heparin, its rate of disappearance, or calculated space of distribution between control and treated groups. PHLA was depressed (p less than 0.05) by approximately 50% during long-term estrongen-progestin therapy. PHLA disappearance was similar in both groups. Thus, reduced PHLA in women receiving long-term oral contraceptive therapy cannot be related to altered heparin metabolism or to accelerated enzyme disappearance from plasma. Long-term estrogen-progestin administration may decrease the heparin-facilitated release of individual triglyceride hydrolase activities or enhance the affinity of enzyme binding to tissues.


Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women. A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.


Nonsuppressability of gluconeogenesis by glucose in septic patients. The contribution of alanine to the synthesis of glucose and the oxidation of alanine was evaluated in normal and septic patients using (14C)L-alanine. The data indicate that there is a twofold increase in the conversion of alanine into glucose in sepsis and, further, this increase was observed while the patients were receiving a constant glucose infusion (100 mg/min) prior to and during the single injection of (14C)L-alanine. Failure of glucose to decrease this gluconeogenic response in these septic patients clearly indicates that the controlling mechanism for glucose synthesis is modified following injury and undoubtedly plays a role in the abnormal carbohydrate metabolism observed in injury. The contribution of alanine carbon to oxidation was the same in the control and septic group as measured by the per cent of the (14C)L-alanine dose expired in 3 h. Since the control subjects received glucose continuously during the study with and without amino acids, it is clear that nutritional intake and injury has minimal effect on the oxidation of alanine. This suggests that transamination is not affected by sepsis nor is there an inhibition of pyruvate oxidation following sepsis.


Hypercalcemia in acute uremia and following citric acid administration: differential effect on parathyroid gland microtubule content. Hypercalcemia, which occurs 4 hr after bilateral nephrectomy in normal rats, is not seen 4 hr after either bilateral ureterotomy or sham surgery. These results indicate that it is loss of renal mass per se, not the uremic syndrome, which is responsible for the hypercalcemia. Citric acid levels also increase 4 hr after nephrectomy, and a degree of hypercalcemia and hypercitricemia comparable to that which follows nephrectomy can be produced by administration of citric acid to normal rats. In an attempt to evaluate the role of the parathyroid gland in the development of hypercalcemia in these two situations, the microtubule content of parathyroid gland chief cells was determined by ultrastructural sterologic techniques 4 hr after either bilateral nephrectomy or citric acid administration. The results of these measurements indicate that parathyroid gland chief cell microtubule content increases after citric acid administration but not following bilateral nephrectomy. The significance of these results is not clear. However, since a previous study has suggested a correlation between increased microtubule content and increased secretory status in the chief cell, one may speculate that increased microtubule content resulting from citric acid administration may also be associated with increased parathyroid hormone secretion. By this formulation, citric acid-induced hypercalcemia would be secondary to increased parathyroid hormone secretion, but the transient hypercalcemia that occurs after nephrectomy would take place in the absence of an increase in parathyroid hormone secretion. In this latter instance, it is possible that loss of the kidney, a major site of parathyroid hormone removal from plasma, leads to an increase in circulating parathyroid hormone level, and hypercalcemia, in the absence of an increase in hormone secretion rate.


Effect of intravenous glucagon on urinary catecholamine excretion in normal man. We have evaluated intravenous glucagon as pharmacologic stimulus to adrenal catecholamine secretion in normal human subjects. Urinary epinephrine and norepinephrine were measured at two hourly intervals before and after the intravenous injection of saline, 4 mg glucagon, or 0.1 mu/kg crystalline insulin. Urinary epinephrine was increased 2.3-fold over baseline after both saline and glucagon. By contrast, insulin hypoglycemia produced a 24-fold rise in urinary epinephrine. No rise in urinary norepinephrine was detected in any test. Under the conditions of this study, we conclude that epinephrine excreted after glucagon injection is due to the stress of the test itself. In normal man, glucagon either does not stimulate adrenal catecholamine secretion, or the effect is too small to measure. By contrast, in pheochromocytoma, glucagon may be specific for catecholamine secretion, based on data from the literature. In normal subjects, insulin hypoglycemia remains the only proved method for assessing adrenal catecholamine reserve.


Effects of ethanol on carbohydrate metabolism: I. Influence on oral glucose tolerance test. To study the effect of ethanol on glucose tolerance test, a series of experiments were performed on Sprague-Dawley male rats weighing 250 g. After 18-hr fast, each rat was given, at random, the following test substances (one test substance at a time) intragastrically in a volume of 0.5 ml/100 g body weight: saline; glucose 0.75 g/kg (3 kcal); ethanol 0.4 g/kg (3 kcal); and ethanol with glucose. Saline or ethanol alone produced no significant changes in blood glucose or plasma insulin concentrations. Addition of ethanol to glucose load resulted in glucose intolerance as well as a lower and sluggish insulin response when compared to these with glucose load alone. The results suggest that ethanol per se has no effect on blood glucose or plasma insulin. However, when given together with glucose load, ethanol produces glucose intolerance as well as inhibition of glucose mediated insulin response.


Altered insulin and glucagon secretion in treated genetic hyperlipemia: a mechanism of theraphy? The influence of Halofenate therapy on insulin and glucagon secretion was examined in the Zucker rat with genetic endogenous hyperlipemia. Coincident with the lipid lowering effects of Halofenate, the net change in the basal bihormonal axis favored glucagon, with the I/G molar ratio (Insulin/Glucagon) decreasing from 2.72 +/- 0.53 to 0.96 +/- 0.20 during treatment with this drug. Following arginine stimulation the I/G ratio remained reduced at 0.87 +/- 0.13 in Halofenate treated animals, contrasting with the statistically greater ratio of 2.5 +/- 0.55 in control animals. The Halofenate induced state of reduced insulin:glucagon was associated with hypolipemia, postarginine hyperglycemia, and hyperketonemia,-three metabolic parameters characteristic of glucagon excess relative to insulin. It is suggested that the lipid-lowering action of Halofenate in genetic hyperlipemia may reflect the altered bihormonal axis induced by the drug.


The influence of oral glucose loading on the insulin response to i.v. glucagon in children and adolescents. Fourteen children and adolescents with slight constitutional growth retardation (12 males and two females) aged from 7 1/2 to 18 1/2 yr underwent an oral glucose tolerance test (OGTT 1.75 g/Kg followed at 180 min by an i.v.  glucagon injection (0.03 mg/Kg). On a separate occasion these children underwent a simple i.v. glucagon test. Comparing the glucose and insulin response in the two glucagon tests for each child we found that whereas in the single test the blood glucose rose  slowly with a peak at 30 min, in the combined test the peak was at 5 min. The mean peak values were similar (129 and 121 mg/100 ml). The mean peak insulin response in the single test was 70 muU/ml (at 2 min) as compared to 253 muU/ml (at 2 min) in the combined test. Our studies provide further evidence for a direct effect of glucagon on insulin release and that glucose preloading augments this effect, without relation to the concomitant blood glucose concentrations.


Dietary protein intake and dynamic aspects of whole body nitrogen metabolism in adult humans. The constant isotope-infusion method of Picou and Taylor-Roberts was used to study rates of total body protein synthesis and breakdown in adult subjects following acute changes in the level of dietary protein intake. Six healthy adults, four males and two females, were studied after adaptation to dietary protein intakes of 1.5 and 0.38 g of protein/kilogram body weight/day. Dietary periods were from 7 to 15 days duration. 15N-glycine was used as a tracer, and was administered orally for 60 hr at 3-hr intervals, or by continuous intravenous infusion for 48 hr. Results were similar for both routes of isotope administration for the comparison conducted at the higher protein intake. At the 1.5-g protein level the mean N flux was 28.2 mg nitrogen/kg/hr, with total body protein (N x 6.25) synthesis and breakdown rates being 3.0 g/kg/day and 2.7 g/kg/day, respectively. Reducing the protein intake to 0.38 g/kg/day caused an 8% decrease (p less than 0.05) in N flux, a 27% increase (p less than 0.005) in the rate of total body protein breakdown, and a 15% increase (p less than 0.05) in the rate of protein synthesis. Endogenous amino acids were reutilized more efficiently under these conditions. The findings are discussed in relation to the way in which adult subjects adapt to acute changes in dietary protein intake.


Selenoamino acids in tissues of rats administered inorganic selenium. There are conflicting reports in the literature concerning the synthesis of selenoamino acids from inorganic selenium in animals, and this work was undertaken to further investigate this. Pronase digests of acetone powders of liver and kidney tissue from rats administered 75SeO3= were subjected to fractionation by cation exchange chromatography using current methods for separating the various amino acids. Very little, if any, selenocystine was found in the digests. However, good evidence was obtained for the occurrence of 2,7-diamino-4-thia-5-selenaoctanedioic acid. It is suggested that the selenocysteine portion of this compound was formed by the reduction of the selenite to selenide with its subsequent incorporation into the amino acid by the action of serine hydrolase (E C 4.2.1.22). No selenomethionine was found under the conditions of this study.


Myocardial infarction in the familial forms of hypertriglyceridemia. Among 74 hypertriglyceridemic patients who were referred for study because of hypertriglyceridemia, family investigations detected 19 with familial hypertriglyceridemia and 24 with familial combined hyperlipidemia. The frequency of myocardial infarction among adult living hyperlipidemic relatives of patients with familial combined hyperlipidemia was 17.5% (10/57). Five of these relatives had their infarct between the ages of 40 and 50 yr of age, and five before the age of 40 yr. The frequency of myocardial infarction in living hyperlipedemic relatives with familial hypertriglyceridemia was 4.7% (2/43) and was similar to the frequency of myocardial infarction among normolipidemic relatives (4.5%) or among spouse controls (5.2%). Mortality data due to myocardial infarction among relatives of index patients failed to contribute meaningful information.


Gluconeogenesis from glycerol at rest and during exercise in normal, diabetic, and methylprednisolone-treated dogs. Glucose turnover, glycerol turnover, and the rate of incorporation of glycerol carbon into glucose were measured with the tracer technique (primed constant rate infusion) using 2-3H-glucose and 14C-glycerol, at rest and during exercise (treadmill run) in normal (N), alloxan-diabetic (D), and methylprednisolone treated diabetic (MPD) dogs. At rest only 2%-3% of the hepatic glucose output arose from glycerol. Exercise increased gluconeogenesis about ninefold in N dogs and about fourfold in D and MPD animals, yet less than 9% of the elevated glucose turnover was derived from glycerol. There was a direct linear correlation between the rates of glycerol turnover and gluconeogenesis from glycerol at rest and during exercise in all three groups. The slope constants were however significantly different: 0.45, 0.51, and 0.67 for N, D, and MPD dogs, respectively. In vivo the major factor controlling the rate of gluconeogenesis from glycerol seems to be the glycerol supply on which the specific effects of insulin deficiency and glucocorticoid treatment are superimposed. They appear to be of minor importance. A comparison of the glucose turnover measured by 2-3H-glucose with that measured by 6-3H-glucose showed that the activity of the glucose in equilibrium glucose-6-P cycle was threefold higher in D dogs and elevated by 15-fold in MPD animals.


Distribution of sulfur in urine of patients with cystathioninuria before and during administration of pyridoxine. During administration of 400 mg daily of vitamin B6 as pyridoxine hydrocholoride to two patients with homozygous cystathioninuria, cystathionine excretion fell in a characteristic manner. Inorganic sulfate excretion did not change significantly when considered by itself. Total sulfur excretion, determined as sulfate after oxidation, decreased slightly in both patients and this decrease was statistically significant in one. The ratio of sulfate to total sulfur excretion increased significantly in both patients during vitamin B6 administration. The difference between total sulfur and free plus bound or ethereal sulfate is largely accounted for by cystathionine and lesser amounts of N-acetyl-cystathionine. The results indicate that cystathionine sulfur is not excreted other than as sulfate during vitamin B6 administration and support the hypothesis that cystathionase activity is enhanced by pyridoxine, the resultant cysteine, alpha-ketobutyrate, and ammonia being added to large body pools.


[Side effects after stimulation of gastric secretion with pentagastrin (author's transl)]. Application of pentagastrin (by infusion, by intramuscular and subcutaneous injection) in the usual dose of 6 mug/kg/hr revealed a short lasting enhancement in frequency of pulse-rate and a slight rise in blood-pressure (5 to 10 mmHg), which exceeded the alteration of pulserate, in 30 healthy volunteers with normal blood-pressure. The enhancement of pulse-rate is considered as a psychogenic reaction to injection. The reason of the rise in blood-pressure, which immediately occured and was of long standing duration, is a pharmacodynamic effect obviously. An extensive increase in blood-pressure, collaps, bradycardia or tachycardia was not observed during 120 investigations. We were not able to detect any significant changes in a number of components of serum or blood. The influence on the values of SGOT, LAP, urea, the red and white blood cell count as well as on hemoglobin concentration and hematocrit cannot be excluded however.


[Early cancer of the stomach (author's transl)]. Early cancer of the stomach is defined as a carcinomatous degeneration restricted to gastric mucosa and/or submucosa. The size of extension as well as the mode of perhaps previously spread metastases are not taken into account. The addition early is correct as far as the pathologic-anatomical localized findings are concerned. The clinician however associates early besides the idea of timely recognition and therapy with a better prognosis, e.g. real recovery for the patient. Yet, so-called early gastric cancer does by no means imply absolute curing. Therefore it seems to be more pregnant to speak mucosal and/or submucosal cancer of the stomach.