[Block of the main branches of the bundle of His]. The author describes the contemporary data on the ECG picture of the main right branch, the main left branches of His' bundle block and hemiblock of the left anterior and posterior main branches and their combinations with the main right branch of His' bundle block. Pathohistological changes of the conductive system in different forms of the main branches of His' bundle block as well as their influence on cardieac function and circulation were demonstrated. Work capacity of patients with these blocks was noted.


[Congenital complete atrio-ventricular block]. Case-histories and ECG of 23 patients with congenital atrio-ventricular heart block were studied. Most of these were up to 14 years old. In 10 of these patients concomitant congenital cardiac defects were uncovered which in 7 cases were combined with a corrected transposition of the major vessels. A relationship between the localization of the ventricular pacemaker and the clinical picture of the disease. The attacks of the Morgagni-Adams-Stocks disease were, as a rule, observed in patients with the ventricular pacemaker located beneath the bundle of His bifurcation, which manifested itself on the ECG by deformation and broadening of the QRS complex in the form of a complete or incomplete block of one or both of the bundle of His crura. Most patients with circulatory insufficiency suffered from severe concomitant congential cardiac failures or from frequent attacks of the Morgagni-Adams-Stocks disease.


[On the semiology and genetics of keratoglobus (author's transl)]. A report on the pedigree in familial occurrence of keratoglobus in 3 offsprings probably having autosomal, recessive inheritance of this feature. A deviation from the normal axial length of the ball, the anterior chamber depth and the length of the vitreous space could be found by ultrasonography in 4 eyes with keratoglobus.


[Contributions to the surgical technique of external dacryocystorhinostomy (author's transl)]. The authors describe some modifications of the surgical technique of external dacryocystorhinostomy. The preliminary exploration methods and their evaluation are considered. An arched skin incision is used for a more anatomical dissection to approach the lacrimal sac. The following bone trepanation is then made with burrs designed by Burch Barraquer. It should be rather large (15-20 mm), backwards and downwards in the nose bone. A running suture, with three external skin stiches as pexia, is used to tie the anterior muco-mucosal flaps together. This suture is them removed after approximately 12 days. Management and procedures in special cases as well as in reoperations are also discussed.?Author


[Follow-up of cases of suspected glaucoma (author's transl)]. The authors analysed the findings in 280 patients suspected of glaucoma. These patients were controlled over a long period in the course of which 30 developed a glaucoma. The authors recommend the measurement of IOP in all patients in the office so far as there is no contraindication and a 1/2 yearly control of all suspected cases to begin with. They recommend further that after 4 year control the provocative tests should be repeated in case there is yet no manifestation of the disease. Finally they recommend that the pilocarpine-test should be done if the pressure level reaches 26 mm Hg in order to fish out cases of manifest glaucoma early enough.


[Ophthalmological medals and coins (author's transl)]. The author - a collector of ophthalmological medals - made a list of all ophthalmological medals and coins that he could find. In this cataloguq he does not only mention the memorial and prize medals of ophthalmologists but also those of physicists, physiologists, surgeons, opticians who have made a name in the field of ophthalmology. Further ophthalmological congress medals and badges are presented.


[Fixation-test using the Heine-mini-ophthalmoscope with regulation of intensity of illumination (author's transl)]. A report on experiences with the Heine-mini-ophthalmoscope with gliding regulation of intensity of illumination for fixation test in children employing a fixation object newly developed by K. Heilmann.


[Phase-difference haploscope with a varioobjective for the measurement of aniseikonia (author's transl)]. The author reports on a technical modification of Author's phase-difference haploscope. Through the employment of a varioobjective pictures of size variation ranging from +60 percent to -30 percent could be continually used for the measurement of aniseikonia. Through this the range of fusion of patients with aniseikonia could be measured under conditions of aniseikonia. The importance of the variation of the size of pictures for the measurement of range of fusion in strabismus is pointed out.


[Scanning electrone microscopic investigations of synthetic suture material (author's transl)]. Alterations of polyamide 6/6 sewing material after ophthalmologic micro-surgical operations were investigated by a scanning electrone microscope. On the basis of the typical transverse fissures of the nylon strings we succeeded in proving that these alterations were similar to those of a stick with circular cross-section after stress deflexion. Thus the fissures of the string cover can be reduced mainly to a mechanical permanent stress.


[Improvement of visual acuity in lens opacities using an optic aperture (author's transl)]. The author reports on improvement of visual acuity in cataract patients through placing a stenopacic opening before the eye. Recommendation is made as to the nature of such a visual aid.


[Spontaneous healing of a malignoma? (AUTHOR'S TRANSL)]. The author reports on the following case: A 46-year-old female patient had an inflammatory lesion of the sclera, similar to an episcleritic nodule, which was treated with cortisone eye drops without success. Because of increasing pigment release in the conjunctiva a malignant neoplasma was suspected. There was no further treatment. After the patient started a treatment of her own in the form of a grape-diet without any other source of nourishment her symptoms disappeared.


[Low tension glaucoma. Contribution to etiology (author's transl)]. A report on a patient with pathological cupping of the disc and visual field defects similar to those found in glaucoma. In the sitting position the IOP was 18 and 21 mm Hg and in lying over 30 mm Hg. This abnormal positional effect was measured with the pneumotonograph which is based on a new principle of applanation independent of position. The classification of glaucoma simplex and low tension glaucoma as well as the differentiation from pseudoglaucoma are discussed.


[An instrument for vitrectomy (author's transl)]. The development of a new vitrectomy instrument has contributed to advancement in vitreous surgery to a large extent. The principle of this instrument is the suction of the vitreous into a needle and its simultaneous resection. In the meantime several constructions have been described. The resection apparatus, observation possibilities and illumination are discussed.


[ERG and EOG results in X-chromosomal vitreo-retinal degeneration (author transl)]. ERG and EOG were performed in three male patients deriving from two no related families and who had vitreo-retinal degeneration including macula area. The EOG was below normal and ERG-potentials particularly b-waves reduced. The finding although of interest are not pathognomically significant. Therefore the diagnosis is only proven by morphological fundus changes and genetics studies indicating a sex-linked transmission.


[Orbita teratoma in a new-born (author's transl)]. An orbital tumor of the size of an apple with a centrally placed optic vesicle was removed in a new-born baby girl 3 days after delivery. The histological examination revealed a mature teratoma with derivatives of all blastodermic layers. There has been no relapse up till now and the further growth of the girl has not been impaired.


[The coats of the eyeball and the intraocular pressure (author's transl)]. The coats of the eyeball influence the results of tonometry 1. by their response to changes of intraocular volume and pressure as expressed by the deltaP/deltaV-ratio and 2. by the rigidity of the cornea. None of the clinical methods in use is able to measure the true deltaP/deltaV-ratio in vivo. Therefore this factor has to be either eliminated from tonometry or measured by a rather complicated new procedure as described in this paper. The rigidity of the cornea as measured on enucleated eyes, offers a resistance increasing significantly with the thickness of the cornea, the size of the applanation and the altitude of the intraocular pressure. It might be neglected in applanations up to 3 mm in diameter, in larger applanations however it becomes a remarkable source of error.


[The effect of gamma rays on glutathion and ascorbic acid content in rabbit lenses (author's transl)]. It is pointed out that the partner non radiated eye is also influenced after employment of high radiation on an eye. The authors radiated rabbit eyes with gamma rays employing Stallard-applicators and determined the glutathion and ascorbic acid content in the lenses. The lenses of the partner eye were also examined for comparison. In those eyes which were directly radiated there was a fall of concentration of the two substances indirectly proportional to the dose of rays employed. In the partner eyes which were not directly subjected to direct radiation there were changes of similar character which were however not so much pronounced. The role of glutathion and ascorbic acid in lens metabolism is pointed out.


[Orthostatic cephalic hypotension and the eye (author's transl)]. The pressure in the ophthalmic artery was measured during change of posture from the lying position to the sitting position by means of Muller's ophthalmodynamometer. In 210 healthy individuals there was a fall of average pressure between 0 and 21 percent. In 89 patients having a certainly pathological fluctuation of 25 percent or more which could not be found in the brachial pressure. Such patients did not only have general orthostatic symptoms but also various ocular symptoms.


[Tonography test according to Leydhecker. Clinical comparison by tonography according to Grant (author's transl)]. In our 1st series of examinations the Grant's 4-minutes-tonography, combined with waterdrinking (Becker), was compared with Leydhecker's modification of 7-minutes-tonography. Out of 60 healthy eyes were 13,3% false-positive with the 4-minutes-tonography, combined with waterdrinking, however with the 7-minutes-tonography none of these were glaucoma-suspicious. For 92 glaucoma-suspicious eyes, which were tested with both methods, the 7-minutes-tonography proved to be much more valuable. Leydhecker's value P3/CL3-7 offers 38,4% positive results at a starting pressure of 18-22 mm Hg, and 51,1% positive results at a starting pressure of 20-24 mmHg. Grant's 4-minutes-tonography, combined with waterdrinking (Becker), may show suspicious values at pressures of 18-22 mm Hg, however is not able to register with certainty existing pathological findings. In 2nd series of examinations 54 eyes with proven glaucoma chronicum simplex were tested with the 7-minutes-tonography. It showed a reliability of 83%.


[A comment on siderosis bulbi (author's transl)]. Report on a case of advanced siderosis bulbi. Besides the typical alterations in the anterior segment of the globe, siderotic changes of the retina could be revealed. The ERG showed a reduction of the b-wave. After removal of the foreign body, a partial regression of the siderotic changes took place. In addition, the ERG became normal within 8 weeks postoperatively. The indication for removal of metallic intraocular foreign bodies despite specific alterations of the ERG is emphasized.


[A new possibility for the measurement of cyclophoria and cyclotropia with the glascyclometer (author's transl)]. The glascyclometer is used for measuring cyclophoria and cyclotropia in free space with and without influencing the gained experience in the area of gaze for near and far as well as in head tilting. The apparatus is easy to handle. The reliability of results of measuring and their easy reproductability are of special advantage.


[A case of unilateral endogenous intraocular mycosis through candida parapsilosis (author's transl)]. The clinical course of a unilateral intraocular mycosis through candida parapsilosis is described. The fungus could be histologically verified from a whitish yellow thick deposits on the lens in the anterior chamber after enucleation of the eye. The ocular infection was endogenic probably through an infested cava-catheter.


[A case of isolated bilateral microcoria and ectopic lens (author's transl)]. The author reports on a patient having a congenital bilateral microcoria and ectopic lens. This is a not yet described combination of isolated abnormalities which are normally combined with other symptoms of Marfan-syndrome. This isolated ocular manifestation is to be regarded as a maldevelopment of ectoderm.


Breeding nude (nu/nu) mice.

Breeding nude (nu/nu) mice. By using as sires homozygous nude males bearing thymus glands from their normal siblings, heterozygous females yield 50 per cent nu/nu offspring under conventional conditions.  Most nu/nu females are fertile, but in our experience only 20 per cent of them rear nude litters to weaning age.


Differences in blood values depending on age in laboratory-bred European hampsters (Cricetus cricetus L.). No significant differences in blood parameters were found between males and females aged 13-900 days.  A comparison of the various age groups showed significant differences in the number of erythrocytes, leucocytes, thrombocytes and in the diameter of red blood cells.  The number of erythrocytes and leucocytes was lowest, and the erythrocytes had the largest diameteres in young animals.  The number of thrombocytes was lowest in older animals.


Effect of litter size on milk yield in the rat. The amount of milk removed from rats during 1 hour's suckling after a separation period of 8 hours was estimated by weighing their pups.  In the 1st experiment litters of 9 pups were suckled by all rats.  At test sucklings held daily on days 6-15 of lactation, pups were reallocated to give 3, 6, 9, 12 or 15 pups per dam.  The largest amount of milk was removed at suckling by groups of 12 pups. In a 2nd experiment, rats were constantly sucked by litters of either 3, 6, 9, 12 or 15 pups from birth to slaughter at 15 days post partum.  Rats with 12 and 15 pups yielded the most milk, nearly twice as much as those suckling only 6 or 9 pups.  Litters of 3 pups consumed less than 1/3 of the amount consumed by litters of 6 or 9 pups.


Some pathogenic aspects of murine sarcoma virus (Moloney) in rats. The oncogenic effect of the murine sarcoma virus (Moloney) was tested in rats.  Host-age and virus-dose dependent variations in the pathogenic spectrum were found.  Four tumour "stages" were described: progressively lethal; lethal after long stationary period; complete tumour regression; tumour reoccurrence after complete regression.  Virus recovery was highest from the progressively growing tumours and in the reoccurred neoplasms, while no virus was found in stationary tumours or in those sites where regression had occurred.  Tumour onset and death was more rapid and frequent when inoculation of the virus was in muscle-rich tissues.  When inoculation was into different visceral organs or intravenously, tumour development still occurred primary in muscle tissue.


Pulmonary artery sling.

Pulmonary artery sling. Pulmonary artery sling is an uncommon and potentially lethal vascular anomaly that can produce airway obstruction. Despite the availability of a corrective operation, the mortality rate remains very high (50 per cent of surgically treated children) due to the high incidence of associated obstructive anormaliies of the tracheobronchial tree. The survivors of corrective operation have done well symptomatically. However, when restudied, most have been found to have no pulmonary blood flow to the left lung. Successful treatment requires early recognition of the anomaly, adequate preoperative investigation for associated anormalies (especially those of the tracheobronchial tree), a technically perfect vascular reconstruction, and meticulous postoperative respiratory therapy.


Thoracic surgical problems associated with rheumatoid arthritis. Nine cases are presented that represent nearly all of the pleural, lung, and pericardial manifestations of rheumatoid arthritis. Three of the 9 had lung biopsies for various reasons to confirm the presence of the rheumatoid change. Six patients had complications of the disorder that required thoracic surgical intervention. The operations included emergency exploration of an empyema cavity for hemorrhage, decortication of the heart and lung, permanent open empyema drainage, and tube thoracostomy. The fact that all of the patients withstood the major complications and major surgery proves that patients with severe rheumatoid disease can withstand major thoracic surgery whenever there occurs a problem that will further increase their disability or threaten their lives.


The association of carcinoma of the esophagus with achalasia. Among 156 patients with achalasia who were treated during a 13 year period, two developed squamous cell carcinoma of the esophagus. The first, a 33-year-old man, developed a carcinoma of the upper third of the esophagus 2 years after the onset of symptoms of achalasia. He was treated by a Heller myotomy and radiation therapy and survived 16.7 months. The second, a 60-year-old man, had had symptoms of achalasia for 15 years. He is alive with suspected recurrence 6 months after undergoing esophagogastrectomy for a carcinoma of the middle and lower thirds. A summary of the literature regarding carcinoma complicating achalasia is presented. This indicates that carcinoma arises in at least 1 to 7 per cent of patients with achalasia. Delay in diagnosis is common. The treatment need not differ from that of carcinoma without a chalasia, but the prognosis is dismal. Since there is evidence that retention esophagitis is a premalignant condition, it should be possible to prevent the development of carcinoma in achalasia by early cardiomyotomy in cases in which hydrostatic dilatation is not completely effective. A plea is made for closer surveillance of patients with achalasia so that, if carcinoma supervenes, it may be detected at an early stage.


Total sequestration of the right lung.

Total sequestration of the right lung. A 2-day-old baby with severe respiratory distress and cyanosis was admitted to the hospital with a totally opacified right pleural cavity. Preoperative studies demonstrated absence of the right pulmonary artery, and a patent ductus arteriosus, and a left pulmonary artery pressure of 85/45 mm. Hg. The hypoplastic right lung received its entire blood supply from multiple vessels through the diaphragm. The infant's condition improved initially after a right pneumonectomy, but she died of progressive respiratory insufficiency at the age of 7 months.


Runaway pacemaker in seven patients: a persisting problem. Runaway pacemaker has been encountered in 7 patients during the past 7 years at the Texas Heart Institute. In this series, 4 patients with fixed-rate pacemakers experienced pacemaker arrhythmias because of battery depletion, and 3 had arrhythmias because of component failure. Battery deterioration was heralded by an increase in cardiac rate. Ventricular tachycardia, rapidly followed by ventricular fibrillation, occurred in 2 patients. Prompt surgical exteriorization of the failing pulse generator and connection to an external pacemaker resulted in prompt recovery in all patients. Elective generator change should be performed routinely after 24 to 30 months unless reliable serial observations of ventricular rates can be attained. This at least will reduce the lethal complications attributed to battery exhaustion. Increasing developments in the design of generators and sources of power, as well as data from pacemaker clinic follow-up and telephone pulse transmittal, are expected to decrease the frequency of this complication.


Pulse duration variation and electrode size as factors in pacemaker longevity. For the past 4 years, we have used highly efficient Medtronic electrodes (Nos. 6901 and 6907), with small surface areas, for cardiac pacemakers. We have found that chronic thresholds average 1.6 Ma. at a 1 msec. pulse duration, compared to 4.9 Ma. for the conventional Medtronic No. 5816 electrodes. These electrodes have been used in association with Medtronic Models 5961 and 5931, ventricular-inhibited and asynchronous pulse generators in which output current and voltage are fixed and pulse duration is variable. Drain from the generator battery is directly related to impulse duration and is reduced at shorter durations. The strength-duration curve of cardiac stimulation suggests and actual long-term pacing has been achieved at an average of 0.2 to 0.3 msec., rather than the conventional 1.0 msec. Drain from the battery is one fourth that of pacemakers of 1970 and one half that of present day, conventional units. This fact suggests that a realistic average life of the pulse generator is 4 years or more.


Effects of obstruction of cardiac lymphatics. A study was undertaken in the dog to determine whether changes occurred in the lymphatics of the endocardium and myocardium of both ventricles after obstruction of the cardiac lymphatics. Other investigators have reported ventricular subendocardial hemorrhage, increased elastic and fibrous tissue in the left ventricle endocardium, and opacification of the mitral valve leaflets. In 14 experiments the ventricular walls were injected with India ink. The efferent cardiac lymphatics were followed to their termination in the cardiac lymph node or nodes. These nodes were excised, as were afferent and efferent lymphatic trunks. After 4 to 16 weeks, with the aid of extracorporeal circulation and oxygenation, biopsies were taken of the myocardium and endocardium of the ventricles of the beating heart. Six animals were used as control subjects. Grossly, there were no changes in the endocardium, myocardium, or valve leaflets. Light and electron microscopy demonstrated no fibrosis or elastosis, and no lymphatics were identifiable. We were unable to establish evidence of permanent changes as a result of obstruction of the lymphatics of the dog heart.


Cavernous hemangioma of the heart: case report and review of the literature. A case of diffuse cavernous hemangioma of the heart discovered incidentally during life is reported. Resection of the tumor was impossible at operation. Two similar cases were found in the literature. Radation therapy is suggested, and the importance of a simple blood pool scan in the investigation of paracardiac masses is stressed.


Neurogenic influences on the coronary vascular response to ischemia in the awake dog. The influence of the nervous system on the response of the coronary vessels to ischemia was evaluated by observing the reactive hyperemia subsequent to a 10 second occlusion of the left circumflex coronary artery in 19 awake dogs. Sympathectomy produced by pretreatment with 6-hydroxydopamine, chronic total surgical cardiac denervation, beta-adrenergic blockade with propranolol, and alpha blockade with phentolamine did not significantly after the reactive hyperemic response. Thus cardiac denervation did not impair the ability of the coronary vasculature to respond to a brief ischemic stimulus.


Isolated, unruptured sinus of Valsalva aneurysm: serendipitous detection and correction. Reaction of an isolated, unruptured sinus of Valsalva aneurysm is described. Detection was serendipitous in a patient with previous surgical resection and grafting of significant aortic coarctation. The philosophy and importance of proceeding with elective resection in these progressive lesions is emphasized.


Partial anomalous systemic venous return: report of surgical treatment in two cases. Two cases of anomalous systemic venous return were correctly diagnosed preoperatively and repaired by intracardiac baffle. These cases are of interest because of their anatomy, embryology, and the surgical method chosen to correct them.


Aorto-pulmonary shunt in the premature infant: technical considerations. In a 13-day-old, 1,300 gram premature infant with tricuspid atresia, a Potts-Smith anastomosis was successfully performed. We used a neurosurgical vessel clip, smaller than the smallest available vascular clamp, to side-clamp the descending aorta. This report appears to be the first of the construction of a Potts-Smith shunt in an infant of this size.


Extracorporeal perfusion for acute respiratory failure: recent experience with the spiral coil membrane lung. Selection criteria, clinical data, and physiological measurements obtained during five extracorporeal membrane lung perfusions for acute respiratory insufficiency are presented. Four patients died and 1 survived. A new technique of femoral artery cannulation to allow aortic arch perfusion is described. When properly monitored, this route provides improved oxygen delivery to the brain during venoarterial (VA) perfusion. The importance of monitoring the equivalent of carotid artery Po2 during VA perfusion is emphasized. Recognition of the effects of high cardiac output in limiting the quality of extracorporeal perfusion, plus the use of hypothermia to reduce output, are stressed. We have confirmed that perfusion can be accomplished with small quantities of heparin, so that bleeding is reduced, but thrombocytopenia and occasional hemorrhage continue to be persistent problems.


Interventricular septal defects from penetrating injuries of the heart: a report of 12 cases and review of the literature. In the past 7 years, 1967 through 1973, 12 patients who had interventricular septal defects from penetrating stab wounds of the thorax were treated at Detroit General Hospital. In 10, the defects were confirmed by cardiac catheterization. Four of the 12 patients were symptomatic and required surgery. Two of these patients had pulmonary-to-system flow ratios less than 2:1. Both these patients had left ventricular dysfunction as a result of coronary artery and myocardial damage from the penetrating trauma to the left ventricle. One of the 4 patients had an injury to the tricuspid valve; this is the first reported case of a traumatic interventricular septal defect associated with a left ventricle-right atrium shunt and tricuspid valve insufficiency. Another patient had a laceration of the left anterior descending coronary artery, in addition to the interventricular septal defect. Ligation of the injured artery resulted in a left ventricular aneurysm. Three patients had "multiple defects" in the muscular septum which proved to be a single interventricular septal defect in which the left to right shunt was divided into multiple jets by the trabeculae carneae of the right ventricle.


Distribution of oxygenated blood in experimental perfusion via the femoral and carotid arteries. The efficiency of femoral and carotid artery perfusion was compared in 10 dogs. The purpose of our study was to determine under what conditions the femoral artery can be used to perfuse the upper body satisfactorily during prolonged perfusions.


Treatment of intercostal neuralgia with 10 per cent ammonium sulfate. Intercostal nerves were injected with 10 per cent annomium sulfate in 41 patients (52 total sets of injections) for management of intercostal neuralgia from radical mastectomy (six blocks), thoracotomy (20 blocks), or unknown etiology (26 blocks). Five patients failed to return for follow-up evaluation and could not be located. Sixty per cent (28/47) of the treatments produced complete or nearly complete (excellent) relief of pain. Excellent pain relief persisted for more than 20 days after 22 treatments and for more than 90 days after seven treatments. Postblock neuritis never occurred. We conclude that intercostal nerve block with 10 per cent ammonium sulfate effectively relieves intercostal neuralgia and is not associated with postblock neuritis. We therefore believe that ammonium sulfate nerve blocks should be administered for treatment of intercostal neuralgia before phenol or alcohol nerve blocks or a surgical procedure.


Nature of deposits in a tubular membrane oxygenator after prolonged extracorporeal circulation: a scanning electron microscope study. Although silicone fibers are among the most compatible with tissue and blood, numerous deposits are observed after their prolonged usage in a capillary membrane oxygenator, even when the blood has been properly heparinized. The scanning electron microscope (SEM) study shows that the morphology of these deposits varies greatly, depending upon the part of the unit from which the sample is taken. The area close to the inlet is the most severely affected. The outlet zone is affected to a lesser degree, and the areas in between are only slightly affected.


The action of carbon dioxide on the collateral pathways of pulmonary ventilation. The major collateral ventilatory pathways between the segments of the lobes of the dog are lined with smooth muscle and course from bronchiole to alveolus and from bronchiole to bronchiole. In previous studies, we showed that the channels constricted with metacholine and dilated with epinephrine. Carbon dioxide elevations in the inspired air, as noted in this study, greatly increased the collateral flow, whereas 100 per cent oxygen did not affect it. The greatest dilatation occurred when the inspired carbon dioxide increased from 2.5 to 6 per cent, with little if any further change when increased to 15 per cent. When perfusion of the in situ lung was blocked, or when the lung was excised, carbon dioxide still had a marked bronchodilating effect. This indicates its direct action on smooth muscle. The fact that carbon dioxide acts as a dilator of the collateral channels, independent of neural and humoral influences, confirms its important role in ensuring maximal pulmonary ventilation.


Prolonged perfusion with a membrane oxygenator in awake ponies. Prolonged extracorporeal membrane oxygenation (PEMO) was performed in 6 adult ponies with the membrane oxygenator in vein-to-artery bypass circuit. A flow rate equal to 46 per cent of control cardiac output was diverted through the PEMO circuit of 10 to 24 hours. Three of the 6 ponies were perfused for at least 20 hours and developed no complications. Immediately following initiation of PEMO, left ventricular output decreased; however, in the interval between 6 and 24 hours, left ventricular output was increased above control levels. Aortic pressure and left ventricular work were markedly elevated during PEMO. Pulmonary ventilation and oxygen uptake also decreased initially but were elevated during later stages of bypass. Pulmonary compliance did not change, except in those studies in which problems were encountered with perfusion techniques. Hepatic glycolysis and hyperglycemia occurred and were more severe in ponies with catheter-produced thrombi. Marked diuresis, which could be attributed only partially to the hyperglycemia, was present throughout PEMO. Based on the minimal morphologic changes observed in the ponies, extracorporeal circulation diverting one half of the cardiac output through a membrane oxygenator can be safely performed for up to 24 hours.


Changes in arterial pressure, viscosity and resistance during cardiopulmonary bypass. Large changes in arterial pressure and systemic vascular resistance are frequently observed at the onset of and during cardiopulmonary bypass, particularly when hemodilution is employed. In order to assess the extent to which these changes are induced by changes in blood viscosity, we measured viscosity, pressure, and flow in a series of 17 patients. Hemodilution was used in Group A (12 patients) but not in Group B (5 patients). At the beginning of cardiopulmonary bypass, the arteriovenous pressure difference decreased an average of 53.8 per cent in the Group A patients, concomitant with a 41.7 per cent decrease in blood viscosity. The arteriovenous pressure difference in the Group B patients increased an average of 6.4 per cent, while the blood viscosity increased by 8 per cent. A nomogram was theoretically derived for the Group A patients, which allows rapid estimation of the extent of viscosity-induced hypotension for a given volume of priming fluid, initial patient hematocrit, and patient weight. After correction for viscosity changes due to hemodilution, the Group A patients were found to exhibit essentially normal values of systemic vascular resistance at the start of bypass, with a mean of 1,155 dynes-sec./cm.5. On the other hand, the Group B patients had elevated resistance values, with a mean of 1,611 dynes-sec./cm.5. During perfusion, the resistance of both groups tended to increase, sometimes by 100 per cent or more. In some cases, however, the resistance values changed in an erratic fashion. These effects were not due to changes in blood viscosity.


Mitral valve replacement with a turtleneck-disc prosthesis. A 5 year experience in 100 patients with a turtleneck-cuff (Magovern) disc valve (Harken) is presented. The prosthesis was inserted into the atrioventricular position by a continuous suture technique. The operative mortality rate was 7 per cent and the late mortality rate, 8 per cent. Age, functional classification, multiple valve replacement, pulmonary hypertension, and reoperation did not influence the operative mortality rate. However, the incidence of late death was much higher among patients in Class IV than in Class III and was also greater when more than one valve was replaced. The incidence of combined early and late thromboembolic complications was 7 per cent. Peribasilar leaks or valve dehiscences were not encountered.


Transvenous atrial pacing with a new electrode. The unique concept of an atrioventricular electrode is presented. This transvenous electrode is incorporated into one body and has the mechanical advantages of double fixation and atrial or ventricular sensing or pacing. With the "extension wire principle," it can be used for diagnostic or therapeutic purposes, short- or long-term pacing. The optimal pacemaker setting can be adjusted according to the individual needs of the patient and can easily be converted to a permanent system. This atrioventricular electrode was used for long-term atrial pacing in 4 patients with tachyarrhythmia syndrome. There were no electrode-related complications. Atrial pacing was maintained in all patients. The longest follow-up period was 2 1/2 years.


Tricuspid atresia with christmas disease (hemophilia B). Report of a case. A case combining Christmas disease and tricuspid atresia is presented. A severe coagulation defect in a hypoxic, polycythemic patient poses an added grave risk to major surgery. In the presence of marked and worsening symptoms, however, major surgery can be performed in these difficult cases. Close liason with a skilled hematology department is essential. Minimal tissue dissection is advised, and the usefulness of a reversed saphenous vein conduit is described.


Macroscopic enzyme-mapping verification of large, homogeneous, experimental myocardial infarcts of predictable size and location in dogs. Difficulty is frequently experienced in producing a large homogeneous myocardial infarct in the dog heart because of the extensive network of coronary anastomoses. This problem may be overcome by combining the ligation of the left anterior descending coronary artery with agar injection into the distal coronary vasculature to obliterate anastomotic channels. All infarcts produced in this manner occupied a constant area in the anterior wall of the left ventricle. From our results in 25 dogs, the individual infarct averaged 12.3 Gm. in weight (range 9.4 to 13.5), representing 25 to 30 per cent of the total left ventricular muscle mass. The homogeneity of the infarct was verified by a simple, macroscopic enzyme-mapping technique based on the inability of the ischemic (dehydrogenase-deficient) myocardium to reduce triphenyl tetrazolium chloride and by detailed histologic studies. Apart from providing ample raw material for comprehensive morphologic, chemical, histochemical, and radioisotopic analyses, a large myocardial infarct also serves as a useful experimental model for various physiological and hemodynamic studies of cardiogenic shock and left ventricular akinesis.


Internodal conduction. Immediate and long-term effects of transverse circular incision of right atrium including atrial septum. Immediate and long-term effects of a transverse circular incision of the entire right atrium, including the atrial septum, on internodal conduction were studied in 7 dogs. Electrocardiograms were followed up to 35 weeks, and the atrial epicardial excitation sequence was evaluated in all 7 dogs. The findings were compared with data from 3 normal dogs and 3 other dogs which underwent total atrial transverse incisions. All dogs with total atrial separation developed complete atrioventricular (A-V) block immediately after the operation and died within 3 days. All dogs with right atrial interruption exhibited persistent sinus rhythm with slight extension of P-R intervals and a normal QRS immediately after the operation. The mean P-R interval reached its maximum at the fourth day (50 per cent increase), remained prolonged through the first week, but returned to near control valves after 12 weeks. Three days later developed transient arrhythmia; sinus arrhythmia; sinus arrhythmia in 2 dogs and second-degree block in 1 appeared between the tenth and fourteenth postoperative days. Postoperative P vectors migrated toward the left. Atrial excitation sequence studies demonstrated prolongation of atrial epicardial conduction intervals (2.3 times) between the sinus node and distal right atrial wall. The presence of an interatrial conduction mechanism (whether by specific pathways or not), through which sinus node excitation was transmitted to the A-V node was demonstrated.


Surgical management for acute coronary insufficiency with three year's follow-up. In this report, acute coronary sufficiency is defined as unstable angina requiring narcotics for relief and an unstable electrocardiogram with or without transient mild enzyme elevations. Forty-five consecutive patients with this syndrome underwent coronary artery grafting with the saphenous vein within 48 hours of the onset of symptoms. They were followed for 3 years. There was an 8.8 per cent operative mortality rate. One long-term survivor sustained a fatal myocardial infarction 18 months postoperatively. One nonfatal myocardial infarction occurred 6 weeks postoperatively. Therefore, the 3 year cumulative mortality rate was 11 per cent and the 3 year myocardial infarction rate was 4 per cent. Thirty-eight patients are in Class I clinical status, 1 is in Class II, and 1 is in Class III.


The profile and surgical management of mitral stenosis in young patients. Mitral stenosis in the younger age groups in India is a unique condition characterized by a short duration and a rapid progression of symptoms. The majority of patients with this lesion develop pulmonary hypertension at an accelerated pace, and about one third have associated congestive failure and functional tricuspid regurgitation. Five hundred consecutive patients with this condition were treated surgically, 493 with a closed valvotomy. The over-all hospital mortality rate of 5.8 per cent was related to the severity of the preoperative functional status. In the last 150 cases, the figure dropped to 2 per cent. Assessment during the first 5 years after surgery revealed an excellent functional status in 85 per cent. The incidence of restenosis was only 3.4 per cent in the first 5 year period and 11 per cent in a subsequent 6 to 10 year follow-up period. Twenty of the 21 subjects with restenosis had an excellent functional result following closed transventricular valvotomy, and this status has been maintained during the follow-up period. To our knowledge, there are no other reports of long-term follow-up data in young patients undergoing surgical treatment for mitral stenosis.


The effect of different methods of protecting the myocardium on lysosomal activation and acid phosphatase activity in the dog heart after one hour of cardiopulmonary bypass. The present study was undertaken to determine the involvement of cardiac lyososomes in injury to the myocardium after cardiopulmonary bypass. Twenty conditioned mongrel dogs, weighing 15 to 18 kilograms, were fasted overnight, anesthetized with sodium pentobarbital (30 mg. per kilogram), intubated, and maintained on positive-pressure ventilation. The femoral artery and femoral vein were cannulated for pressure measurements. After median sternotomy, intravenous heparin was administered (3 mg. per kilogram) before the aorta and the superior and inferior venae cavae were cannulated for bypass. Bypass was instituted with a Travenol modular pump and a Bentley pediatric bubble oxygenator and heat exchanger. The ultrastructural effects on the myocardium and the acid phosphatase activity in the left ventricle were compared in dogs exposed to bypass for 1 hour with varying types of myocardial support: perfusion of the coronary arteries, normothermic ischemic arrest, or selective cardiac hypothermia. The morphology of control hearts and hearts fixed after 1 hour of coronary perfusion were similar. The distribution and structure of subcellular lysosomes were the same and showed identical patterns of acid phosphatase activity. Normothermic ischemic arrest was associated with a loss of glycogen stores, disrupted sarcoplasmic reticulum and T tubules, vacuolization and decrease in matrix density of mitochondria, and separation of the intercalated discs. Lysosomal activity was absent except for occasional residual bodies in the nuclear pole zone of the myocardial cells. Selective cardiac hypothermia produced results superior to those from normothermic ischemic arrest. Although these hearts showed proliferation of the lysosomal compartment, the organelles responsible for excitation-contraction coupling were spared.


Stimulation tests for diagnosis of medullary thyroid carcinoma. We compared the maximal calcitonin secretion produced by pentagastrin, calcium, and glucagon for preoperative detection of medullary thyroid carcinoma in four subjects with normal or slightly increased plasma immunoreactive calcitonin (iCT) levels. In each case, pentagastrin administration produced higher peak iCT levels (5- to 36-fold increases over basal) than did calcium infusion (by 1.9- to 10.3-fold) and glucagon administration (by 3.6- to 27.4-fold). These preliminary studies suggest that pentagastrin is an effective agent for use in rapid stimulation tests designed to detectmedullary thyroid carcinoma in asymptomatic patients who have normal basal iCT concentrations.


Summated auditory evoked potentials in the cerebellum and inferior colliculus in the young rat. The summated auditory evoked responses recorded at the superior surface and depth of the cerebellum of the young rat had a similar latency and configuration as did summated auditory evoked potentials in the inferior colliculus. Electric stimulation of the inferior colliculus did not evoke a response (other than the shock-artifact response) at the cerebellum. Stimulation of the cerebellum did not modify the evoked responses to click in the inferior colliculus (unless current levels were large enough to cause current spread to the brain stem). There is insufficient evidence to conclude that the cerebellum has an auditory receiving area in the young rat.


Fluttering of atrioventricular valves in patients with d-transposition of the great arteries after Mustard operation: an echographic observation. Postoperative echocardiograms were obtained in conjunction with cardiac catheterization in 14 patients with d-transposition of the great arteries who had undergone the Mustard operation. All 14 patients had atrioventricular valve fluttering demonstrated echographically, although the degree and type of fluttering of both valves varied in each patient. Significant tricuspid valve fluttering was not demonstrated in two patients. Atrioventricular valve fluttering was not related to any one hemodynamic residual. The study suggests that atrioventricular valve fluttering was related to the relatively restrictive atrial tunnel, resulting in turbulent blood flow across these valves. Two patients with d-transposition of the great arteries who underwent repair by the Rastelli operation (without an intra-atrial baffle) did not have atrioventricular valve fluttering.


Thyroid radioiodine uptakes and scans in euthyroid patients. A substantial increase in the dietary iodide intake in many communities has caused a major increase in the total iodide pool in the body and a consequent decrease in the normal thyroid radioiodine uptake. Because of the pronounced regional variations in iodide supplementation of food, and because the effects of this additional dietary intake on radioiodine uptake are so large, a redefinition of the normal range of thyroid radioiodine uptake values in patients seen at this institution was thought to be indicated. The results of 6-hour and 24-hour thyroid radioiodine uptake studies in 44 euthyroid subjects, with scan data on the 20 who were studied with 123-I, are consistent with other reports indicating that the current normal thyroid radioiodine uptake values are lower than those accepted several years ago.


Changes in plasma renin substrate, plasma and renal renin, and plasma osmolarity during glycerol-induced acute renal failure in rabbits. Seven groups of rabbits were studied before or at various intervals after the subcutaneous administration of 50 percent glycerol in isotonic saline (14 ml/kg).  A sharp increase in plasma crystalloid osmolarity, due to glycerol reabsorption from the subcutaneous tissue, was detected at 1.5 and 6 hours and was maximal between 12 and 20 hours.  Plasma renin activity did not change at 1.5 hours, but it was significantly elevated at 6 hours and maximally increased between 12 and 20 hours.  The increase of plasma crystalloid osmolarity might contribute to renin release in this experimental model.  Changes in renal renin levels after the administration of glycerol were not significant, although lower renal renin values were consistently found in rabbits with more severe impairment of renal function.  Plasma renin substrate increased later than plasma renin activity (20 hours) and remained high after plasma renin activity had returned to normal (48 hours).  The increase of plasma renin substrate was interpreted as mainly due to the impairment of renal function, since a positive correlation was found between plasma creatinine and plasma renin substrate.


Influence of primary bile acid feeding on cholesterol metabolism and hepatic function in the rhesus monkey. In three healthy rhesus monkeys fed chenodeoxycholic (chenic) acid, there was no consistent increase in the total exchangeable cholesterol pool or input to the cholesterol pool.  In three similar monkeys fed cholic acid, the total exchangeable pool increased in all animals and input to the cholesterol pool increased in two.  Serum glutamic-pyruvic transaminase (SGPT) increased transiently in two animals in each group.  Morphologic abnormalities (triaditis with atypical ductular proliferation) were noted in one animal; this animal was ingesting chenic acid but had normal liver test results at the time of biopsy.  Biliary bile acids contained 8 to 14 percent lithocholic acid in the chenic acid group and 48 to 72 percent deoxycholic acid in the cholic acid group.


An unusual compressive syndrome of the cauda equina. An unusual case of a capillary hemangioma of the filum terminale is presented.  The successful removal returned the patient to an asymptomatic state.


Nitrogen metabolism in bears: urea metabolism in summer starvation and in winter sleep and role of urinary bladder in water and nitrogen conservation. Three bears were studied under conditions of (1) no food but access to water for 2 weeks and (2) no food or water for 3 weeks. During starvation in summer, the bears could not inhibit the net production of urea but used lean body mass; when denied access to water as well, the bears became dehydrated and azotemic. Urea was continuously formed and degraded in the winter. Arginase activity in liver increased in winter sleep; hepatic steatosis and inflammatory reactions were also noted. The urinary bladder readsorbed labeled urea and D20 in winter; the rate of absorption of urea was equal to the rate of excretion of it into the bladder. The ability to preserve lean body mass during winter sleep apparently is a special mechanism associated with the induction of winter sleep. Bears cannot duplicate this feat during summertime starvation. In winter sleep, urea is formed and degraded but the nitrogen produced is conserved in some manner that maintains the total nitrogen pool constant. The urinary bladder plays a central role in maintaining the state of winter sleep by absorbing water and solute at a rate equal to their entry into the urinary bladder.


Pancreatography in the diagnosis of carcinoma of the pancreas. Until recently the pancreas was regarded as one of the most diagnostically unapproachable organs. Tests of function were for the most part indirect, and results tended to be misleading. Endoscopic pancreatography has proved useful in the investigation of diseases of the pancreas and the biliary tree, and has become routine in several gastroenterology centers around the world. Experience with the procedure in patients with suspected carcinoma of the pancreas is reviewed.


Role of liver scanning in the diagnosis of hepatic metastases. Liver scanning is quite useful in detecting metastases, particularly when none are suspected clinically, and obviates the need for more elaborate and expensive examinations in about half the cases in the series analyzed here.


Diagnostic approaches in metastatic lung disease. Procedures such as bronchoscopy, bronchial brushing, pleural needle biopsy, mediastinoscopy, and percutaneous aspiration and trephine needle biopsy afford the specialist in pulmonary medicine a wide diagnostic armamentarium and considerable flexibility in the diagnostic management of patients with metastatic lung disease.


Current philosophy in treatment of primary cancer of the breast. In response to widespread public and professional controversy over the treatment of primary carcinoma of the breast, an attempt is made to assemble a series of facts that most authorities will agree on, to evaluate the threads of consistency that run through most clinical studies, to develop an overall conceptualization of the disease process, and to place these in the context of contemporary medical management and societal attitudes.


Changinc concepts in malignant melanoma. Melanoma currently offers challenges to the medical profession. Opportunities for early detection, development of rational immunotherapy, and gains in curability are unparalled because of the recently defined aspects of early recognition, its cutaneous location, the long periods of superficial lateral growth, the increasing incidence, and the many fascinating immunologic aspects of melanoma.


Changing epidemiology of lung cancer. Increasing incidence in women. Recent worldwide reports show a large increase in the incidence of lung cancer in both men and women. To detail changes in the epidemiology of lung cancer relating to the incidence in men and women, we reviewed the patterns of diagnosis of 1145 patients with lung cancer seen at the Lahey Clinic between 1956 and 1972, during which time the proportion of all men and women seen was unchanged. The total number of women with lung cancer increased greatly and has almost doubled during this period. Lung cancer in women is now increasing at a faster rate than in men so that the male to female incidence has decreased from 6.8/1 (1957 to 1960) to 2.4/1 (1969 to 1972). We reviewed in detail the case histories and pathology of 231 women with lung cancer. No significant change was evident in cell type distribution during the study years. The most frequently seen tumors in women were adenocarcinoma (31 per cent), undifferentiated large cell cancer (22 per cent), epidermoid carcinoma (16 per cent), and undifferentiated small cell carcinoma (12 per cent). Among those women with known smoking histories, the group most responsible for the recent increase in women with lung cancer was comprised of smoking women in whom Kreyberg group 1 (smoking-related) tumors developed.


Immunologic approach to cancer therapy.

Immunologic approach to cancer therapy. The resistance that many cancer patients show to the progress of their disease, attested to by well documented cases of spontaneous regressions as in neuroblastoma, hypernephroma, choriocarcinoma and malignant melanoma, and the long-term dormancy of multiple metastases seen particularly after removal of a primary mass, can be explained only by host defense mechanisms. Attemps at immunotherapy over the years are reviewed and new directions are presented.


Growth kinetics of solid tumors. Implications for chemotherapy. More precise definition of the cytokinetic parameters of human tumor growth will clearly help both in predicting the outcome of disease in individual patients and in planning the dosage schedules of single chemotherapeutic agents and combinations of agents to achieve optimal results.


Recent thoughts on the development of colorectal cancer. Considerable evidence demonstrates that a relationship may exist between adenomatous polyps and carcinoma. While the evidence may be circumstantial, it is not unimpressive. A recently completed 18 year follow-up of patients with benign polyps initially fulgurated demonstrates a statistically significant higher incidence of the development in colorectal carcinoma in these patients than in the unaffected population.


Management of Hodgkin's and non-Hodgkin's lymphomas. These diseases of the lymphoreticular system with neoplastic alteration of the involved tissues represent different entities and show marked variability in their clinical manifestations, pathologic behavior, prognosis, and response to treatment. New diagnostic, histopathologic, and therapeutic concepts in the past decade have led to significant advances in the care and management of these patients, particularly those with Hodgkin's disease.


Hypercalcemia and malignant disease.

Hypercalcemia and malignant disease. Virtually any malignancy may lead to hypercalcemia, but carcinoma of the breast, myeloma, and carcinoma of the lung are especially frequent offenders. A more difficult diagnostic problem is posed by the "silent" tumor which secretes a substance causing hypercalcemia. Foremost in this category are bronchogenic carcimona and hypernephroma.


Fluid and electrolyte problems in patients with advanced carcinoma. Brief outlines of these problems serve to suggest some etiologic factors in their production. The patient seldom presents with a single or simple cause or solution. The body reacts with compensations or side effects, and suffers complications and mixed disorders -- all of which probabilities must be investigated and appreciated before rational therapy can be initiated.


Cancer of the thyroid.

Cancer of the thyroid. These relatively infrequent tumors intrigue both clinican and researcher. Each histologic type posesses its own distinctive natural history, controversy surrounds therapeutic programs, and prognosis is influenced by multiple factors, varying from a fatal outcome within a few months to a nearly normal life expectancy. Since fatalities do occur in patients with well differentiated cancers, a more aggressive approach to all thyroid nodules would improve current survival rates.


Neurosurgical treatment of pain caused by cancer. While pain can be a most useful symptom, it becomes a problem requiring attention when it causes or increases the patient's anxiety, prevents sleep, or starts the patient on a vicious cycle of increasing doses of narcotics with concomitant depression, anorexia, and lethargy. Various surgical modalities and their indications are discussed.


Indications for neurosurgical intervention in metastatic lesions of the central nervous system. The broad spectrum between highly malignant metastatic tumors and more favorable, slow-growing, even solitary lesions makes it impossible to establish rigid criteria for deciding whether to operate on a metastatic lesion. The major objective is to prolong life and function without adding to the patient's pain or discomfort.


Infections in the immunosuppressed patient. Infections in the immunosuppressed cancer patient are caused by a wide variety of bacteria, viruses, fungi, and protozoa; many of these in the normal individual are saprophytes but will cause disease in the immunosuppressed patient, often with treatment failure. Patterns of infection are recognized, and this should enable the physician to plan a meaningful course of action when infection occurs in the compromised host. Obviously, it would be much better to prevent rather than have to treat infection in these immunosuppressed patients. Ideally, in the future, it is hoped that drugs which have less suppressive effect on defense mechanisms will provide a partial solution to the problem of infection in the immunosuppressed patient.


Effects of administration of hypolipidemic agent, 2,2'''- [ (1-methyl-4, 4-diphenylbutylidene) bis (p-phenyleneoxy)] bistriethylamine oxalate (SQ 10,591) upon cholesterol esterification by aorta, adrenal, and testes of cholesterol-fed rabbits]. Administration of 2,2'''-([1-methyl-4, 4-diphenylbutylidene] bis(p-phenyl-eneoxy]) bistriethylamine oxalate (SQ 10,591) at 20 mg/Kg daily for 5 days to cholesterol-fed rabbits resulted in no change in aortic microsomal cholesterol esterification with a palmitoyl coenzyme A substrate or of aortic mitochondrial cholesterol esterification with a palmitate substrate. Esterification by both reactions in the adrenal was much higher than in either aorta or testes. Adrenal and testicular mitochondrial esterification and testicular microsomal esterification were inhibited significantly after SQ 10,591 administration. In vitro addition of 0.0001 M SQ 10,591 significantly inhibited both microsomal and mitochondrial cholesterol esterification in aorta, adrenal, and testes.


Lipid and fatty acid composition of testes of quaking mice. Testes of quaking mice (sterile mutants) and of controls were analyzed for major lipid classes and fatty acid composition. Of the main lipid classes, only cholesterol esters differed significantly in concentration between the two groups (1.01 for quakers vs 0.69 mg/g wet wt of tissue for controls). The concentration of triglycerides was 4.5-5.0 that of total phosphatides 18-19 and that of free cholesterol 1.9-2.0 mg/g for mutants and controls. The concentrations of phosphatidyl ethanolmanine and of sphingomyelin were both lower in quaking than in normal mice, but only the change in the former was statistically significant. Phosphatidyl choline was the major phosphatide (43-45% of total phosphatides) followed by phosphatidyl ethanolamine (24-26%) and sphingomyelin, phosphatidyl serine, and phosphatidyl inositol (all ca. 7% of total phosphatides). Minor differences between the mutants and controls were observed in concentrations of fatty acids of major lipid classes. The mutants, sterile because of faulty spermatid differentiation, had normal quantities of 22:6 w3 and 22:5 w6. These data are consistent with the hypothesis that the 22-carbon polyenes are associated with the formation of spermatids, rather than with their final differentiation into spermatozoa.


Separation of polyunsaturated fatty acids by argentation thin layer chromatography. A single step, silver nitrate thin layer chromatographic procedure which separates a methyl ester mixture containing 0-6 double bonds is described. Purity of each ester recovered from the silver nitrate plate was 98-99%. Recovery of the esters ranged from 100% for saturates to 77% for pentaenes.


Simple, rapid method for detecting phase transititons of lipids. A simple rapid method was worked out for studying the physical and structural state of lipids by measuring the refractive indices of a layered lipid film. Melting processes of n-paraffins and phase transitions of phospholipids and the lecithin-cholesterol system also can be followed as a function of temperature. In accordance with data from the relevant literature, the measured refractive indices show that cholesterol lowers the phase transition temperature  of lecithin. By isorefraction curves, the most ordered structure of the layers is indicated to occur at the equimolar ratio of cholesterol and lecithin. The method may be applied to study the effect of lipid-soluble agents upon lipid structure and is applicable for routine investigations and industrial purposes as well.


Hydrocarbons from males, females, and larvae of pecan weevil: Curculio caryae (Horn). As part of a program to identify as many as possible of the components of the pecan weevil, Curculio caryae (Horn), the hydrocarbons from males, females, and larvae were isolated by solvent extraction and column chromatography and subjected to gas lipuid chromatography-mass spectrometry analysis. n-Alkanes from C14-C32 in the larvae and unsaturated and branched chain hydrocarbons from C20-C32 in males and females were found. There are no significant differences between the hydrocarbons of the male and female pecan weevils.


Effect of dietary linolenic and linoleic acids upon growth and lipid metabolism of rainbow trout (Salmo gairdneri). Nine diets, each containing different levels of linoleic acid (18:2 omega 6) and linolenic (18:3 omega 3) were fed to duplicate groups of rainbow trout for 14 weeks. The growth rate, feed efficiency, accumulated mortality, and fatty acid composition of neutral fat and phospholipids of these groups of fish were determined. The growth was slow in the groups of fish receiving diets containing (A) low concentration of 18:3 omega 3and (B) high concentration (5%) of 18:2 omega 6. The accumulated mortality was high in these groups of fish. The diet containing 1% of 18:3 omega 3 alone supported rapid fish growth with low mortality . The feed efficiency of this diet was also high. The metabolism of 18:2 omega 6 and 18:3 omega 3 in fish and their conversion to more unsaturated fatty acids typical of fish lipids was investigated.


Nature of alkanes in beef heart lipids.

Nature of alkanes in beef heart lipids. n-Alkanes have been found to be the major saturated hydrocarbon components in the fatty tissues on beef heart. These alkanes consist of a homologous series C14-C35, with the C29 and C31 n-alkanes being most abundant. C16, C19, and C20 isoprenoid alkanes also were identified. A C17 isoprenoid alkane tentatively was identified. The fatty tissues on beef heart contained 32 mug/g saturated hydrocarbons. The distribution pattern of these saturated hydrocarbons is in marked contrast to the alkane distribution in beef liver where branched and cyclic alkanes are predominant. The enrichment and the similarity of the n-alkane distribution in the fatty tissues on heart and in pasture plants may have implications for the physiological aspects of hydrocarbons in the diet.


Studies of lipid class and fatty acid profiles of rat mammary tumors induced by 7, 12-dimethylbenz(a)anthracene. The lipid class and fatty acid composition profiles of mammary glands of female rats fed a nutritionally adequate diet are compared to those of tumors induced in the mammary glands by intravenous injection of  dimethylbenz(a)anthracene of animals fed the same diet. Ca. 95% of the lipids of the mammary glands of the control group of animals consisted of triglycerides; glycolipids and phospholipids were present in only minor amounts. In contrast, the lipids of the mammary tumors contained much lower amounts of neutral lipids and higher concentrations of phospholipids. The glycolipid fraction was a minor component of both tissues but differed greatly in composition. The composition of the phospholipid and neutral lipid fractions, particulary the latter, of the mammary tumors also differed from that of the mammary glands of the control animals. The neutral lipids of the tumor tissues contained elevated levels of free fatty acids and cholesterol and much lower concentrations of triglyceride compared to the mammary gland lipids. Differences also were observed in the fatty acid composition of tumor and mammary gland lipid. The greatest differences occurred in the concentrations of polyunsaturated fatty acids which were generally much higher in the tumor lipids.


On methylating activity of L-(methyl-14C)-methionine in metabolism of phospholipids by insect Ceratitis capitata. The methylating activity of L-(methyl-14C)-methionine in different stages of developmenent of the insect Ceratitis capitata was studied in a series of in vitro and in vivo experiments. Larval and pharate adult homogenates of the insect were used in the in vitro conditions, and the utilization of the methyl group of methionine for the synthesis of different classes of phospholipids was evaluated. Incorporation of radioactivity in lipids by pharate adult homogenates was significantly higher than that by larval homogenates. In both cases, phosphatidyl ethanolamine showed the highest levels of radioactivity incorporation. Free bases from total lipid hydrolysates were resolved and identified by paper chromatography, and the labeling was investigated by radioactivity scanning of paper chromatograms. Significant differences were observed in the activity of both stages of development of the insect. Larval and pharate adult homogenates incorporated mainly the labeled methyl groups into ethanolamine. Monmethyl ethanolamine was the only methyl derivative that appeared in the hydrolysates of lipids synthesized by larval homogenates, whereas mono-,di-and trimethyl ethanolamine clearly were detected in those synthesized by pharate adult homogeneates. Administration of L-(methyl 14C)-methionine to larvae confirmed the existence of methylation reactions in the metabolic activity of the insect.


Sterol metabolism: XXXIII. On derivation of cholesterol 7-alkoxyl ethers. The facile acid-catalyzed conversion of cholest-5-ene-3 beta, 7 alpha-diol (but not of cholest-5-ene-3 beta, 7 beta-diol) in methanol or ethanol solution to the corresponding 7 alpha-methyl or 7 alpha-ethyl ethers and epimerization of the 7 alpha-alkyl ethers to the corresponding 7 beta-alkyl ethers were established. The epimeric cholest-5-ene-3 beta, 7-diols, their 7-methyl ethers, and their 7-ethyl ethers are readily interconverted in acidified solvents, the quasiequatorial 7 beta-epimer predominating in each case. Both 7 alpha- and 7 beta-alkyl ethers may be encountered as artifacts in analyses of sterol mixtures from mamalian tissues.


Comparison of lipid composition of Aedes aegypti and Aedes albopictus cells obtained from logarithmic and stationary phases of growth. The total lipids, total neutral lipids, and total phospholipids from Aedes aegypti and aedes albopictus cells cultivated in vitro in a medium containing fetal calf serum were analyzed. The mosquito cells were harvested in the logarithmic and stationary phases of growth. The fatty acid profiles of the lipids showed differences during the aging of the cells but not betweeen species. There was an increase in chain elongation and unsaturation of the fatty acids in the stationary phase when compared with the logarithmic phase of growth. The major components of the fatty acid profiles of the cells were 16:0, 16:1, and 18:1 fatty acids. Few similarities were found between the lipid analysis of the mosquito cells and the growth medium.


Aplastic anemia following viral hepatitis: report of two fatal cases and literature review. Within recent years the combination of aplastic anemia following viral hepatitis has been reported with increasing frequency suggesting the existence of a causal relationship between the two conditions.  Two case histories of aplastic anemia following hepatitis are presented in detail, and the information on 193 such patients reported in the literature through 1972 is summarized.  A number of parameters were evaluated and extensive cross correlation carried out in order to define criteria which might have diagnostic, prognostic or therapeutic value.  Males were more likely to develop bone marrow failure following hepatitis (p congruent to 0.05), but females were less likely to survive the marrow depression (p smaller than 0.025).  No other statistically identifiable criteria were detected.  The hematologic changes commonly encountered in hepatitis are reviewed.  These and other observations support the concept that subclinical hepatitis may be responsible for a significant percentage of so-called idiopathic aplastic anemia, for which, at present, no etiology can be determined in nearly half the cases.  Possible pathogenetic mechanisms are discussed as they might relate to chromosomal abnormalities which were found in one of our patients.  It is suggested that occasional fortuitious human infection with animal viruses known to be both hepato- and myelotoxic could relate the hepatitis and aplasia.


Mucosal neuroma, pheochromocytoma and medullary thyroid carcinoma: multiple endocrine neoplasia type 3. 1. Three members of a kindred and a fourth unrelated individual demonstrating the syndrome of mucosal neuroma, bumpy lips, marfanoid habitus, medullary thyroid carcinoma and pheochromocytoma are reported, and the literature pertaining to this syndrome has been reviewed. 2. There are currently 41 definite and 16 additional probable reported cases manifesting the syndrome of mucosal neuroma, bumpy lips, pheochromocytoma and medullary thyroid carcinoma.  Mucosal neuroma was present in all patients.  Medullary thyroid carcinoma was histologically proved in 38 cases.  Pheochromocytoma was documented in 19 patients with a probable diagnois in another 4 patients.  Only one patient was noted to have hypercalcemia associated with parathyroid adenoma.  Associated abnormalities seen in this syndrome include hypertrophied corneal nerves, skeletal defects and gastrointestinal tract abnormalities.  3. The relationship of this syndrome to other types of multiple endocrine neoplasia syndromes and the phakomatoses is also discussed.  This syndrome appears to be distinct from the entity of multiple endocrine neoplasia type 2.  We suggest that this syndrome be called multiple endocrine neoplasia type 3, following the classification originally proposed by Steiner et al.  4.  MEN type 3 appears to be inherited as an autosomal dominant disorder.  Many apparently non-familial cases have been reported, but due to inadequate information regarding family history it may be possible that some of these cases also had other affected family members.  5.  This syndrome most likely results from a dysplasia of neuroectodermal tissue.  The pathogenesis of this syndrome is discussed and evidence supporting the hypothesis is reviewed.  6.  The importance of diagnosing the syndrome at an early stage and of investigating the relatives of a patient manifesting this potentially fatal syndrome are stressed.  7.  Plasma calcitonin measurement following calcium infusion is extremely useful as a screening procedure for the diagnosis of medullary thyroid carcinoma, when the patients are completely asymptomatic and routine thyroid function tests are normal.  Affected individuals should also be periodically screened for the development of pheochromocytoma.


The starved kidney: a defect in renal concentrating ability. The renal tubular responsiveness to antidiuretic hormone was assessed in seven obese patients during starvation and feeding by an overnight dehydration test followed by exogenous vasopressin. All seven subjects showed a mean reduction of one-third in their maximum urinary osmolality on day 4 of starvation. Thes- data show that the renal tubule is partially insensitive to antidiuretic hormone at a time when it is also insensitive to mineralocorticoids.?Author


The metabolic balance technique: a critical reappraisal. Twenty-six metabolic balance studies (MBS) of Ca, Mg, and P have been conducted in 11 postmenopausal women with osteoporosis and in 4 patients suffering from Paget's disease of bone. Subjects were given a liquid formula diet (LFD) matched as closely as possible to the patient's home diet. Studies lasted for 25 days, separated into 5-day periods by a carmine marker combines with Cr2O3 as continuous fecal marker. The balance studies were combined with a tracer technique using 47Ca to detect a possible loss of Ca by perspiration. The reliability of analytical methods necessary for mineral balances was tested. In 22 of the 26 MBS a steady state (SS) reflecting the patient's regular living conditions was demonstrated, while a non-SS situation possibly due to changes of physical activity was seen in four instances. The overall precision and accuracy of this balance method for Ca and P was found to be better than plus or minus 50 mg/day after four periods and plus or minus 40 mg/day after five periods, as related to an average daily intake of 920 mg Ca and 1230 mg P. For Mg (intake 190 mg/day), a precision of plus or minus 10 mg/day was recorded. The dermal loss of Ca was found to be less than 20 mg/day. As shown for Ca, Mg and P, the precision of a balance study is only little enhanced when the investigation is continued for more than four periods. At the present time is not possible to predict non-SS situations before starting such a study but a simple formula is proposed to detect those which were not performed under SS conditions.


Uric acid kinetic studies in the immediate post-myocardial-infarction period. The etiology of hyperuricemia following myocardial infarction was investigated by uric acid kinetic studies carried out on seven male patients following myocardial infarction and on two control subjects. The patients selected had uncomplicated myocardial infarction and were maintained on a low-purine diet. Measurements of uric acid pool size and turnover rates using 2-C14 uric acid were made, commencing on days 2-5 following myocardial infarction. Initial concentration of serum uric acid ranged from 2.9 to 9.8 mg/100 ml. Uric acid pool size was elevated in six of seven patients. Five had a pool size of from 36.9 to 79.6 mg/kg, while the single gouty subject demonstrated 104 mg/kg compared with 12.6 and 16.8 mg/kg for the control subjects. Turnover rates were also increased, ranging from 1036 to 2772 mg/day (controls, 612 and 872 mg/day). Twenty-four-hour urine uric acid excretions ranged from 358 to 623 mg/24 hr. Serum lactic acid concentration was normal (1.03 plus or minus 0.17 muM/ml), and endogenous creatinine clearance in all cases was 77.9 ml/min or greater. These data suggest that following myocardial infarction there is an expansion of the uric acid pool with an increased uric acid turnover rate. Only the patient with a previous history of gout had uric acid excretion outside the normal range.


Lipid metabolism in pregnancy. II. Postheparin lipolytic acitivity and hypertriglyceridemia in the pregnant rat. Plasma postheparin lipolytic activity (PHLA) has been measured in rat pregnancy to qualitatively assess mechanisms of triglyceride removal from the circulation. This assessment can be made if the larger plasma volume of pregnancy is considered. A supramaximal dose of heparin avoids dilution of the heparin stimulus to PHLA release. Dilution of the released PHLA is corrected using measurements of plasma volume. In addition, no evidence of circulating inhibitors is present, and timing of PHLA appearance is unaffected by pregnancy. Prior studies of postheparin lipolytic activity in human pregnancy have not taken the effect of plasma volume into account and must therefore be reconsidered in light of the present results. We observed a biphasic pattern in PHLA over the course of gestation. Levels were increased in midgestation (day 12), declined to normal by day 19, and fell rapidly to one-half of control by day 21. Assuming a functional role for the triglyceride lipases represented in PHLA, the data suggest the following hypothesis: triglyceride removal is increased or normal for the greater part of gestation and is decreased only at term. If this hypothesis proves true, the hypertriglyceridemia of pregnancy should be due largely to overproduction, with decreased removal contributing only near term.


Metabolic effects of increased caloric intake in man. In order to determine if increased caloric intake could be responsible for the insulin resistance and elevated plasma glucose, insulin, and triglyceride levels commonly associated with obesity, hypercaloric diets were fed for 3 wk to eight normal subjects, and the metabolic consequences of this diet were assessed before significant weight gain had occurred. One wk of increased caloric intake led to statistically significant increases in fasting plasma insulin (22 per cent), glucose (5 per cent), and triglyceride (30 per cent) levels, as well as an increased insulin response (20 per cent) to oral glucose. Since the average weight gain during this period was only 1.6 kg, the observed changes appear to be secondary to increased caloric consumption, not obesity. Most of these changes returned toward baseline values during the succeeding 2 wk of increased caloric intake, but statistically significant elevations of fasting plasma glucose (10 per cent), insulin (8 per cent) and cholesterol (15 per cent) levels were still seen at the end of the hypercaloric dietary period. On the other hand, insulin resistance, as estimated by direct measurement of insulin responsiveness, did not change as a result of 3 wk of increased  caloric intake. These results indicate that acute increases in caloric intake can lead to elevated plasma glucose, insulin, cholesterol, and triglyceride levels. These changes occurred before significant weight gain had taken place, and raised the possibility that at least some of the abnormalities of carbohydrate and lipid metabolism attributed to obesity may be due to increased caloric intake. However, this conclusion would not seem to apply to the insulin resistance associated with obesity, as 3 wk of increased caloric intake did not produce any change in the responsiveness of these subjects to insulin's action.


The effects of acute and chronic dexamethasone administration on insulin binding to isolated rat hepatocytes and adipocytes. In an effort to determine the possible relationship between changes in insulin-receptor binding and the glucocorticoid-induced insulin-resistant state, we studied insulin binding to specific receptors located on isolated adipocytes and hepatocytes obtained from dexamethasone (D)-treated rats. Three groups of D-treated rats were studied: (1) acute high-dose treatment (1.5 mg/kg/6 days), (2) acute low-dose treatment (0.125 mg/kg/6 days), and (3) chronic low-dose treatment (0.125 mg/kg/21 days). When insulin binding to isolated hepatocytes was studied, we found that binding to isolated hepatocytes was studied, we found that binding was only 30%-50% of control values when cells from the D-treated animals were used. This decrease in binding was greatest for cells from the acute high-dose group, indicating a dose-response effect, and least for cells from the chronic group, suggesting a tendency toward return of insulin-receptor binding during chronic treatment. When insulin binding to isolated adipocytes was studied, binding was 50%-60% of control values when cells from both acute D-treated groups were used. While the magnitude of the decrease in insulin binding was not as great as that seen with hepatocytes, the decrease was still greatest using cells from the acute high-dose group as compared to the acute low-dose group. Thus, a dose-response effect was suggested in both tissues. On the other hand, the effects of chronic D treatment on insulin binding were strikingly different in the two cell systems. After chronic D treatment, insulin binding to adipocytes returned to near-normal levels, while a 55% decrease in binding to hepatocytes persisted. Thus, the tendency toward return of insulin binding after chronic D treatment seen with hepatocytes was almost fully expressed by adipocytes. This might be related to the amelioration of the corticosteroid-induced insulin-resistant state which has been reported after chronic corticosteroid administration to humans. In conclusion, (1) a decrease in insulin binding is associated with corticosteroid excess, and it is possible that this decreased binding is related to the insulin resistance which results from corticosteroid administration; (2) the return of insulin binding toward normal after chronic D treatment could well be related to the improvement in insulin resistance seen during chronic corticosteroid administration to humans; and (3) the difference in effects of chronic D treatment on insulin binding to hepatocytes versus adipocytes indicates that changes in insulin binding can be tissue specific.


Colchicine: effects upon urinary hydroxyproline excretion in patients with scleroderma. Three patients with scleroderma were given intravenous infusions of colchicine (2-4 mg/day) for 3 days. Twenty-four-hour urine collections were assayed for total hydroxyproline (HYPRO), an index of collagen resorption, and for nondialyzable polypeptide HYPRO, an index of collagen synthesis. During the colchicine infusions there was a fall in total urinary HYPRO and a slight increase in the per cent nondialyzalbe HYPRO in each patient. The hydroxylysyl-galactosyl-glucose (HGG) to hydroxylysyl-galactose (HG) ratios were not strikingly different in two samples, with the greastest differences in HYPRO excretion. Our results suggested that total body collagen catabolism had diminished without a concomitant decrease in synthesis. In contrast to provocative reports in the literature, these data do not support the hypothesis that administration of colchicine in doses tolerated in man can either inhibit synthesis of new collagen, increase degradation of mature collagen, or be of use in treatment of fibrotic states.


Correlation of serum triiodothyronine (T3) and thyroxine (T4) with biologic effects of thyroid hormone replacement in propylthiouracil-treated rats. To study the role of T4 to T3 conversion in the biologic action of T4, thyroidectomized, hypothyroid rats were given subcutaneous T4 (0.8 or 1.6 mug/100g/day) with or without intraperitoneal propylthiouracil (PTU) (1 mg/100g/day). Rats were killed after 5, 10, 12, or 15 days of treatment and serum T3 and T4 levels were correlated with serum TSH, liver mitochondrial alphaGPD activity and weight gain. In rats killed at 5 days, PTU treatment resulted in higher serum T4, lower serum T3, and a markedly elevated serum T4:T3 ratio, demonstrating that PTU inhibits peripheral conversion of T4 to T3 in the rat. Despite higher T4 levels, mean serum TSH was higher in the two groups receiving PTU as well as T4. In rats receiving 0.8 mug T4, growth rate was also slower with concomitant PTU administration. In other groups of rats treated with 0.8 mug T4 for 10 and 15 days, PTU treatment resulted in similar differences in T3, T4, and T4:T3 ratios and serum TSH. At 15 days, rats treated with 0.8 mug T4 mptu had significantly lower alphaGPD activity than rats receiving 0.8 mug T4 alone. PTU treatment had no effect on alphaGPD activity in rats maintained on 0.1 mug T3/100g/day indicating that there was no inhibition of this biologic response to T3 by this agent. PTU without T4 had no significant effect on TSH, weight gain, or alphaGPD activity. In addition, the dialyzable fraction of T3 and T4 in serum was not altered by this agent. These data show that in animals treated with T4, with and without PTU, TSH suppression, alphaGPD activity and growth correlate better with serum T3 concentrations than with serum T4. This suggests that for maximum biologic activity, T4 must be converted to T3.


[Drug therapy in newborns and young babies]. Over the last twenty years drug therapy for the newborn and young infant has developed from its empirical origins to a state where the results of intensive research can be applied. As biochemical studies have shown, enzyme activities and the mechanisms of detoxification are dependent on age. These findings have prompted pharmacokinetic considerations with regard to dosage, especially in repetitive dosage regimens. Further aspects include interference and in particular the protein-binding of drugs in the newborn, side effects of drugs administered to the expectant mother, only seen later in their infants, and side effects characteristic for the newborn. Finally mention is made of some recent advances in pediatric antimicrobial therapy. The most frequent side effect is the inefficiency of drugs because of underdosage.


[Drug metabolism in early life].

[Drug metabolism in early life]. For various reasons the dosage of drugs in early life is difficult and complicated. Besides differences in sensitivity of pharmacological receptors, in protein binding of drugs and in drug distribution the metabolic elimination of drugs has to be considered as playing an important role for the understanding of the pharmacotherapeutic peculiarities of the perinatal period. The most important means for chemical inactivation of drugs are oxidation and conjugation of these foreign compounds. Both pathways will be briefly outlined. Evidence for a decreased ability of infants to oxidize drugs can be found in the observation that the biological half lives of amobarbital and other drugs are about twice as long as those of the mother. Retarded conjugation in infants manifests itself especially with sulfonamides. The postnatal development of the drug oxidizing enzyme system is described with special emphasis on the development of cytochrome P450 in young pigs. In this context it is of interest that the apoenzyme of the mixed function hydroxylase seems to be present already before the iron containing haem moiety is fitted into the enzyme molecule. Furthermore it is described that the postnatal development of the glucuxonyl transferase is different for different substrates.


[Special pharmacokinetic aspects in newborns and young infants]. The safety of drug therapy in the newborn period and early infancy is endangered for two main reasons: 1. The relative distribution volume of drugs during maturation and in pathological states varies greatly and thus makes conventional dosage in short-term therapy ineffective. 2. During early childhood, the rate of elimination of many drugs is slow hence there is a risk of overdosage in long-term therapy with doses considered safe in older children. The example of two drugs demonstrates, that the course of blood levels is not only dependent on the elimination half life and on the relative distribution volume, but may also be modified to a large extent by the process of invasion. This increases the risk of iron-dextrane but contributes to the safety of Cephalexine. If drug therapy is to be safe and effective in childhood at least the basic elements of a most simple pharmacokinetical model consisting of Invasion, Volume of Distribution and Elimination must be known as can be shown by the mathematical extrapolation of blood level curves gained from single applications for long-therm therapy.


[The importance of the albumin bilirubin binding in drug therapy in the newborn]. Bilirubin encephalopathy in the newborn is caused not so much by the level of total serum bilirubin but rather by the level of free bilirubin not bound to albumin. Compared to adults prematures and newborns show a higher tendency towards separation of bilirubin from the albumin bond which is statistically significant as could be demonstrated by measurements in serum and plasma. This might be due to a lower bilirubin binding capacity of the neonatal albumin or a competitive displacement of the bilirubin from the albumin bonds by unknown endogenous substances. The influence of several drugs, of blood exchange transfusion and of light in phototherapy on the cleavage of bilirubin from its albumin bond was examined. Some drugs, but not the phototherapylight, enhanced displacement.


[Familial infantile achalasia in three siblings]. Following the review of the literature "achalasia" in 3 brothers of a family with 5 children is reported. Inherited, acquired, constitutional and circumstantional factors may have a role in the manifestation of this rare illness. Surgical intervention (Heller's esophagocardial myotomy) was effective in the treatment for all three children.


[Anoxic myocardial lesions in man, developed during extracorporeal circulation, studied by electron microscopy]. Anoxemic changes of the myocardium were examined at 20 patients operated on in extracorporal circulation. At a mild degree hypothermia (30 degrees C) morphological changes appear after a 20 minutes period of anoxaemia. Damage to the myocard of irreversible character could be revealed after an anoxaemic period of 43--55 minutes. An intermitting perfusion of the coronary arteries delayes the formation of the lesions, although in cases of ligation of the aorta for 90 minutes severe mitochondrial changes and deformation of cells were seen. The best method for protecting the myocard is an isotherm perfusion of the coronary arteries. Clinical and laboratory findings show that necrosis of the myocard has a focal character and may play a part in formation of postoperative lesions.


[Early ischemic lesion of the myocardium in a case of unusual developmental anomaly of the coronary vessels and coronary thrombosis]. An uncommon form of anomaly of coronary arteries is reported, similar to which had not as yet been published. A single right arteria coronaria was found having an only left branch with a thin vena-like wall, descending on the anterior surface of the heart. The lumen of the sclerotic right arteria was occluded by a thrombus at the point of origin of ramus descendens posterior. The cause of death was an acute cardiac failure, in which authors prescribe an important part to the anomaly of coronary arteries. Areas of myocard getting blood supply from the occluded arteria were investigated by the method of fuchsinorrhagia. Authors believe, that this reaction is suitable for the demonstration of the acute, early ishaemic lesions of the myocard.


[A new method for the study of flow of material into surviving blood vessel segments]. One of the most important questions arising in experiment on surviving segments of vessels is the question of flow of material into the vessel wall through the intima or adventitia. To make a distinction is important for the interpretation of results of in vitro experiments. By using a "tissuephil" tested already in practical surgery wound-adhesive free of any noxious effect, authors could form segments of vessels, having an only intimal or adventitial surface. Using this technique the flow of blood into the wall through intima or adventitia could be investigated separtely. At in vitro experiments most part of the labelled material flows into the vessel wall through the adventitia. This fact can be explained by the presence of microinjuries of the adventitia caused by the removing of the surrounding fat tissue. It is believed that only the flow through the intima gives an information about the condition of the vessels. Flow through the adventitia is mostly artificial.


[Relationship between the thickness of the aortic andventitia and cholesterol and lipid content of blood and aortic wall]. Correlation between the changes of blood cholesterol and lipoid level, exerted by cholesterol feeding and changes of the thickness of the aortic wall was investigated. Changes have been found to be significant, but as it was revealed by investigation of regression no correlation exits between them. Authors believe that thickening of the adventitia in atherosclerosis is a consequence of the morphological changes of the vessel-wall.


[Morphological studies on the hepatotoxic effect of Thiuram (tetramethylthiuram disulphide) in white rats]. After a single per os or a single and repeated subcutan doses of Thiuram necrosis of the liver of different extension was revealed. Changes could be seen by 3--14 days after administration of Thiuram in different doses. In some cases animals died spontaneously. These investigations seems to evidence the fact that Thiuram, which is similar to Disulphiram (Antaethyl-Antabus) used in the therapy of chronic alkoholism in big doses exerts a noxious effect on the liver of white rats.


Melosis as a source of spontaneous mutations in Schizophyllum commune. Spontaneous mutation frequencies were determined for two loci in the fungus Schizophyllum commune, at meiosis and at mitosis.  For both loci the meiotic frequency is significantly higher than the mitotic frequency. No correlation was found between meiotic mutagenesis and recombination of markers bracketing the mutant site.  The meiotic temperature affected the spontaneous mutation frequency but not the recombination frequency in the cross examined. A number of suppressor mutations were detected for both loci examined.  Almost all the suppressors are closely linked to the site they suppress. The distribution of mutations among the suppressor sites was different at meiosis and at mitosis.


Radioresistance in natural populations of Drosophila nebulosa from a Brazilian area of high background radiation. D. nebulosa, collected in two woods of a high background radiation area (both in Iron Hills, State of Minas Gerais, Brazil), were compared to and found to be more resistant than flies collected as controls in two other woods of an adjacent area.  This was the second time that average differences in radioresistance between natural populations were established. Previous experiments were carried out with D. willistoni, in the same area and in comparable fashion.  In spite of their higher radiation resistance the flies from the radiation area carried a higher expressed load than the controls. The following tests were performed to estimate the differences: (a) survival, after whole body exposure to 90 000 R of 60Co-gamma-rays on 120 strains set up from single inseminated females and (b) reproductive performance, in 240 duplicate croses, measured in terms of the difference between irradiated series (males received 3000 R of 60Co-gamma-rays) and their unirradiated counterparts. The data are based on an offspring of 293784 individuals. Futhermore, two diallel crosses between sensitive and resistant strains have shown that the differences probably are due mainly to additive genes.


[Investigations on the mutagenic effect of triethylenemelamine (TEM) on early embryonic tissue and bone marrow of the rat by chromosome analysis (author's transl)]. Female rats were treated with triethylenemelamine (Tretamine; TEM) with a dose of 0.4 mg/kg body weight and 0.6 mg/kg body weight respectively on days 1, 2, 3; 3, 4, 5 or 6, 7, 8 post coitum. The animals were slaughtered on day 9 or pregnancy. Corpora lutea and living and dead embryos were counted to estimate embryonic loss. Thereafter chromosome-analysis of bone marrow cells and embryonic tissue took place. Highter TEM dosage increased the rate of embryonic loss. It increased from 28.1% with a dose of 3 X 0.4 mg TEM to 75.7% with 3 X 0.6 mg TEM. The level of embryonic loss depends on the time of treatment during different stages of early gestation. It was highest on the first 3 days and lowest on days 6-8 of gestation (0.4 mg TEM on -ays 1, 2, 3 p.c., 71.8%; 0.4 mg TEM on days 6, 7, 8 p.c., 2.9%). By the chromosome analysis, early embryonic tissue seemed to be more sensitive to TEM than bone marrow cells. The highest rates of numerical (35.7%) and (3 X 0.4 mg TEM). A higher dose induced a negative dose-effect, the frequency of aberrations decreased (3 X 0.6 mg TEM, 29% NUMERICAL AND 1.2% STRUCTURal aberrations). With increased embryonic loss (from 28.1% to 75%) structural aberrations decreased (from 5.7% to 1.2%). The time of treatment p.c. was highly correlated with the frequency of aberrations. It was highest with TEM application on days 6, 7, 8 of pregnancy; at the same time the mortality rate was lowest. The same tendencies were noted in the investigation of the chromosomes from bone marrow cells.


Cycloheximide resistance in Chinese hamster cells. I. Spontaneous mutagenesis. Resistance to cycloheximide (CHM) was studied in cultured Chinese hamster cells. Concentrations of CHM above 5-10-7 M were toxic for the cells. At concentrations above 9-10-7 M no colonies were recovered in selective medium. 15 resistant clones of independent origin were isolated in selective medium containing 7-10-7 M CHM. Resistance was stable when the cells were cultured under non-selective conditions. The spontaneous mutation rate was determined by the fluctuation test. Mutations to CHM resistance arose spontaneously. The spontaneous mutation rate to CHM resistance was about 10-5.


Human cells repair DNA damaged by nitrous acid. Cultured fibroblasts from normal persons or persons afflicted by xeroderma pigmentosum were used as hosts for adenovirus 2 infection. With xeroderma cells as hosts, nitrous acid-treated virus showed less plaque-forming ability than when normal cells were used, indicating that DNA damaged by nitrous acid is at least partly repaired by normal human cells.