Comparison of indices of muscle and pump performance in patients with coronary artery disease.

During diagnostic cardiac catheterization of 20 patients, 19 of whom had coronary artery disease (CAD), left ventricular (LV) performance was assessed by both muscle function indices and pump function indices. Muscle function indices included max dP/dt, Vpm, Vce5, and Vmax, the latter derived from both total pressure (TP) and developed pressure (DP) using catheter-tip manometry. Pump function indices included LV ejection fraction (EF) and percent abnormally contracting segment (ACS), determined from biplane LV angiography. Muscle and pump function indices were also compared to the presence of the S3 (ventricular diastolic) gallop. Correlations existed between EF and Vmax (TP), EF and Vpm, percent-ACS and Vmax(TP), and percent-ACS and Vpm, with r values of 0.760, 0.777, -0.884, and -0.841, respectively. Vmax(TP) and Vpm also correlated quantitatively with the presence of the S3 gallop (p less than 0.0005). Total pressure-derived muscle function indices appear to adquately describe mean LV performance in patients with CAD and ACS, but these muscle function indices are probably highly dependent upon the size of the myocardial scar.


Systemic heparinization during percutaneous coronary angiography: evaluation of effectiveness in decreasing thrombotic and embolic catheter complications.

Systemic heparinization has been advocated as preventive for thrombotic and embolic complications of arterial catheterization. To test this hypothesis, 95 patients undergoing coronary angiography via the percutaneous femoral arterial approach were randomized into heparinized and nonheparinized groups. Evaluation for thrombotic and embolic complications by clinical means and non-invasive electrical impedance flow measurements in the lower limbs was performed precatheterization, postcatherization, and at 4 and 24 hr. Clinical data reveal loss of distal leg pulses in 11% (5/74) of the nonheparinized group, with two of these individuals developing signs of claudication and requiring embolectomy. No individuals (0/48) in the heparinized group lost distal leg pulses. Immediate, 4-hr, and 24-hr post-catheterization bloodflow was 12%, 10%, and 12% lower, respectively, in the catheterized limb of those in the nonheparinized group. At 24 hr 52% of the nonheparinized group had bloodflow levels lower than the precatheterization levels in the right (catheterized) extremity, while 2% (2/48) of the heparinized group had a similar reduction. One possible complication of excess bleeding was noted with heparin. It is concluded that systemic heparinization is safe and can be an important adjunct in the reduction of thromboembolic complications of percutaneous coronary angiography.


Inotropic action of tolbutamide on human myocardium.

The inotropic action of tolbutamide previously demonstrated in vitro was evaluated in 15 nondiabetic subjects during diagnostic cardiac catheterization. Following bolus injection of 250 mg of tolbutamide intravenously, a rise of serum insulin and a slight fall of serum potassium were observed. Inotropic response was determined from significant fall in PEP/LVET ratio, significant fall of left ventricular end-diastolic pressure, shift to an augmented function curve in work-pressure relationships, and prominent rise of dP/dt values at comparable heart rates. The inotropic effect was greatest at 5-15 min with return to near control values at 30 min. An unusually marked inotropic response was observed in one subject. While the measurable net hemodynamic effect of tolbutamide in the human heart is small, its effect on ischemic and normal areas within the heart of a diabetic patient with atherosclerosis may be different. Thus, its ultimate effect on the diseased heart may be significant.


Cardiac catheterization and selective angiography in infants with a new flow-directed catheter.

Preliminary experience with a new flow-directed pediatric angiography catheter in 35 infants indicates that catheterization of all cardiac chambers and both great vessels can be accomplished without risk of perforation or major arrhythmia. Antegrade access to the aorta from the left ventricle via the foramen ovale reduced the need for retrograde arterial catheterization. The maneuverability of this balloon-tipped catheter coupled with the ability to perform safely selective angiography at any site entered establishes a unique advantage over standard cardiac catheters now in use. The success with this catheter in performing right and left heart studies and the safety in its use promise to significantly reduce the risk of mechanical and angiographic accidents during the intracardiac investigation of critically ill infants with congenital heart disease.


Angiographic estimation of relative coronary artery flow based on terminal branching patterns.

Angiographically "terminal" coronary arterial branches were counted in 100 normal coronary cineangiograms to investigate the possibility that three left ventricular wall regions might be defined by identifying patterns of arterial inflow. An average of 45% of the terminal branches were counted in the anterior region supplied by the anterior descending coronary artery; 25% were counted in the lateral region supplied by diagonal and obtuse marginal arterieistal circumflex and distal right arteries. Based upon the hypothesis that blood flow through an artery is directly proportional to the number of small branches into which it ramifies, this approach affords an estimate of the relative contribution by individual coronary arteries to total left ventricular perfusion. This concept could prove useful in defining a quantitative grading system of coronary arterial inflow obstruction.


Prolapse of the tricuspid leaflets in the systolic murmer-click syndrome.

Right ventriculography was used to assess the tricuspid valve in 61 patients with systolic murmur-click syndrome. Systolic murmurs were present in 47 cases, and 32 had clicks. Mitral valve prolapse was present in 52 patients. Late systolic prolapse of the tricuspid valve was demonstrated in 32 patients (52.4%). In 9 cases, prolapse involved the tricuspid valve alone. In the systolic murmur-click syndrome, prolapse may involve either or both of the atrioventricular valves.


Optimizing cinefilm.

A system for improving the quality of cinefilm and for maintaining quality control is described. Objective criteria for contrast, resolution, and grain structure were established to measure the effects of varying X-ray dose, f-stop, development temperature, and selection of film and developer. We found that all variables nust be adjusted to maximize the viewing quality and that similar denisty curves can be achieved, independently of the choice of film and developer.


Quantification of ventricular performance: a computer-based system for the analysis of angiographic data.

A computer-based quantitative angiography system for the acquisition and analysis of ventriculographic data has been developed. In addition to the apparatus normally required for angiography and left ventricular pressure recording, a digitizing tablet, PDP 11/20 mini computer, and TV monitor with a hard-copy device is employed. Four modes of operation are currently in use: data acquisition, analysis, mini cine, and data tape editor. Data acquisition facilitates forming a magnetic tape record of the digitized pressure, timing, and event identification, together with anywhere from 4 to 100 digitilized LV contours. A number of error checks and feedbacks are incorporated to provide some measure of quality control. In the event an error is written onto the magnetic tape record, the data tape editor can be used to review the record and correct most errors. Analysis of the generated data tape consists of several options which include: pump function, muscle function, pressure derived indices of contractility and systolic time intervals, and contour pattern recognition which is still under development. If the complete analysis option is chosen, a summary of the analysis, referred to as the quick-sight list, is also presented. The so called mini cine option employs a separate and independent acquisition-analysis program. This requires only the end-diastolic (with a segment of wall) and end-systolic contours (without pressure data) to extract the most essential parameters (EDV, EF, CI, HR, and wall mass). As a result of the relative straightforward processing and inherent simplicity, the mini cine option is most frequently used. This system has done much to reduce the time required for analysis of angiographic data, while at the same time maintaining and even improving the quality of the results. Other less tangible benefits include: the possibility to build a readily accessible library of patient data files facilitating a posteriori studies, precise and uniform definition of the rules to input and analyze data, and finally providing a useful step towards fully automatic ventriculographic processing.


Major variations in anatomical origin of the coronary arteries: angiographic observations in 4,250 patients without associated congenital heart disease.

In 51 (1.2%) of 4,250 patients studied by selective coronary arteriography, one or more major elements of the coronary arterial system originated from the sinuses of Valsalva in an ectopic manner. The majority of variations involved the left coronary artery. The majority of ectopic ostia were located in the right sinus of Valsalva. Failure to recognize variations in coronary arterial origin can prolong arteriography procedures and lead to errors in interpretation of coronary artery anatomy and pathology. It is concluded from this experience that the incidence and location of major variations in coronary arterial origin are relatively predictable. The data are useful in expeding coronary arteriography procedures and thus improving patient care.


Thromboembolism associated with pigtail catheters.

Three incidents of asymptomatic arterial thromboembolism associated with polyurethane pigtail catheters occurred during 1,417 cases of left ventricular angiocardiography. No similar incident occurred with polyethylene pigtail or (dacron) Eppendorf and Gensini (style) catheters. In vitro comparison of hydraulic characteristics of polyurethane (Cordis) and polyethylene (Cook) pigtail catheters showed higher flow-pressure transmission through the tip of the Cordis polyurethane catheter favoring dislodgment of any existing clot. The problem of thrombogencity of polyethylene compared with polyurethane remains unsettled. Our experience with polyurethane pigtail catheters has resulted in limitation of their use in our laboratory.


A new atrial septostomy technique.

Balloon atrial septostomy is usually ineffective if the atrial septum is thickened. A technique for incising the atrial septum is described. A no. 6 French catheter was modified to enclose a tiny surgical blade. The distal end of the blade was pivoted to the catheter tip, and the proximal end was attached to a guide wire in the catheter lumen. Advancing the guide wire protruded the blade through a slit in the long axis of the tip of the catheter. Atrial septostomy was performed in five newborn lambs in vivo and in adult dog hearts and human hearts in vitro by advancing the catheter tip across the atrial septum with the blade retracted and withdrawing it to the right atrium with the blade extended. Eight to 12 mm lacerations of the atrial septum were produced and could be extended by subsequent balloon septostomy. The technique may be useful when balloon septostomy has been ineffective.


Measurement of ejection fraction in man by videodensitometry.

This report describes a new method based on roentgen videodensitometry for the measurement of left ventricular ejection fraction in man. The net forward ejection fraction (NFEF) is calculated directly from the formula NFEF=1-exp(-.693/N), where N is the number of cardiac cycles necessary for half of the injected contrast material to be washed out of the left ventricle. The derivation of this formula is presented, and the technique is validated by comparison with washout curves from a Lucite model of the heart and with simultaneous angiographically determined left ventricular ejection fractions in man. The videodensitometry technique offers the following advantages over the conventional volume technique: (1) only a small amount of contrast material is required; (2) ectopic beats are uncommon during the washout phase when measurements are made; (3) the ejection fraction measured is an average of several cardiac cycles; and (4) dependence upon operator interpretation is minimized. Furthermore, given adequate mixing within the chamber, NFEF should be independent of ventricular geometry. Thus, NFEF of the unusually shaped left ventricle can be readily determined.


Percutaneous cannulation of the internal jugular vein for temporary endocardial pacing.

In 148 cases the right internal jugular vein was used as the initial approach for percutaneous insertion of temporary endocardial pacemaker electrodes. Complications were few and none were serious. The technique of percutaneous cannulation of this vein for temporary endocardial pacing is described in detail.


Exercise stress testing in patients with chest pain and normal coronary arteriography: with review of the literature.

Eighty of 654 patients studied because of chest pain were found to have normal coronary arteriography. Fifty of these completed submaximal treadmill exercise studies. The purpose of this study was to determine whether treadmill electrocardiography could obviate the need for coronary arteriography in the evaluation of patients with undiagnosed chest pain. Of patients studied, 22% had typical angina pectoris, while 78% had atypical chest pain. The resting electrocardiogram was normal in 58% of patients, while 42% showed repolarization abnormalities. Submaximal treadmill testing was normal in 64%, incomplete in 12%, and demonstrated classic ischemic S-T depression in 24%. Our findings of 24% positive studies in patients with normal vessels and 12% incomplete tests suggest that stress electrocardiography may be of limited value in predicting the morphologic state of the coronary arteries in patients with undiagnosed chest pain.


Radiation exposure to angiographer during coronary arteriography using the U arm image amplifier.

Radiation exposure to the angiographer was measured using thermoluminescent dosimeters (TLD), commercial film badges, and appropriate ionization survey meters. Data were collected during 47 coronary artery examinations with the lead overleaf. During a single coronary examination, the angiographer receives 0.9 mR to the lens and 2.8 mR to the hand. The calculated yearly exposure to the angiographer performing 10 examinations per week is 450 mR to the lens, 9% of the maximum permissible dose (MPD), and 1400 mR to the hand, 2% of the MPD. Exposure rates for the left anterior oblique (LAD) and right anterior oblique (RAO) projections during cine and fluoroscopy were taken at the position occupied by the angiographer. Scatter radiation is 5-10 times greater in the LAO projection. The second trial was monitored during 18 coronary artery examinations minus the lead overleaf. A significant decrease in radiation exposure was accomplished through the use of the lead overleaf.


Dosimetry of portable image intensifiers in pacemaker insertions.

With the increased utilization of portable image intensifiers for pacemaker insertions, an investigation of the radiation hazards to operative personnel was undertaken. The personnel were tested first utilizing a Rando phantom and later during actual pacemaker insertions. Studies of medical personnel show the critical organs to be the thyroid (approximately 15mR per procedure) and the lens of the eye (approximately 13mR per procedure). While the MPD/week was not exceeded, the radiation dosage was substantial and could increase under operating conditions other than those measured. Recommendations to insure safer operation of this equipment are presented.


Percutaneous transfemoral coronary arteriography without systemic anticoagulation--a review of 648 consecutive procedures.

Experience with 648 consecutive percutaneous transfemoral coronary arteriograms and left ventriculograms performed in a teaching laboratory without the use of systemic anticoagulation during the procedure was reviewed. Only 1 death was felt to be related to a procedure, and this occurred 3 weeks after a myocardial infarction. There were 10 myocardial infarctions or emboli, 8 cerebral vascular accidents, and 7 femoral artery complications. Only 1 patient experienced a residual neurologic change following a procedure-related cerebral vascular accident, and this was a mild visual field defect. Clotting of the catheter without sequelae but necessitating procedural changes occurred in 10 instances. The transient nature of the neurologic deficits and the low mortality suggest that the emboli which occurred in these patients were small, possibly platelet-fibrin accumulations. It is postulated that with the use of careful technic larger emboli capable of producing myocardial infarction with shock or disabling cerebral vascular accidents can be prevented, even in a training situation. However, smaller embolic phenomena probably cannot be completely avoided by the use of careful technic, and it is for prevention of small emboli that systemic anticoagulation with heparin may be of value.


Coronary arteriography: prevention of thromboembolic complications using a pressure-drip flushing technique.

All selective coronary arteriographic examinations (1,833) performed in the authors' laboratory during a five-year period (1/1/70 to 12/31/74) were analyzed for mortality and total morbidity according to method used. During the first two years, the control period, the classic brachial artery cutdown (Sones) and percutaneous femoral artery puncture (Judkins) techniques were utilized. Mortality rate for the total 589 patients was 1.01%. This included a mortality of 0.26% (1/386) for the brachial arteriotomy method, and 2.5% (5/203) for the percutaneous femoral puncture approach. After introduction of the pressure-drip flushing technique, the subsequent three-year mortality rate for a total of 1,244 patients was 0.16%. This included an incidence of 0.17% (1/585) for brachial arteriotomy and 0.15% (1/659) for modified percutaneous puncture techniques. The morbidity incidence during the initial two-year period was 3.0% (18/589). This included an incidence of 2.0% for brachial arteriotomy and 5.0% for percutaneous puncture techniques. After institution of the new pressure-drip flushing technique the total incidence fell to 1.2% equally divided between arteriotomy and percutaneous techniques. Modification of the classic percutaneous femoral artery puncture techniques has resulted in major reduction of mortality and morbidity complications which are chiefly thromboembolic in nature. It has not significantly influenced local thrombotic complications of arteriotomy.


Evaluation of high viscosity contrast media in canine selective coronary arteriography.

A special high viscosity preparation of water soluble radiopaque contrast media was explored in animals for its suitability in selective coronary angiography. The high viscosity required power injection to accomplish adequate filling during selective coronary arteriography. The anticipated angiographic advantages, such as prolonged visualization and coating of the vascular walls, were marginal. Comparison with conventional preparations of the same contrast agent suggests that the high viscosity itself exerts some protective effect with regard to the immediate side effects on the electrocardiogram and mechanical function of the myocardium. However, the high viscosity preparation induced electrocardiographic signs compatible with myocardial ischemia not usually seen to follow the injection of conventional contrast agents. These were followed by mechanical heart failure or ventricular fibrillation resulting in death of 6 of the 10 experimental animals. It was concluded that high viscosity contrast media preparations are unsuitable for use in clinical selective coronary arteriography as presently practiced.


Experience with preformed catheters for coronary angiography by the brachial approach.

Experience with a simplified technique for selective coronary angiography by the brachial cutdown approach using preformed coronary catheters in over 500 cases is described. This technique has facilitated selective catheterization of the coronary arteries in patients where use of the Sones catheter has proven difficult or impossible. Particularly, coronary arteries in patients with a dilated aortic root, high-rising left coronary artery or tortuous subclavian artery are easily catheterized with the preformed catheters described in this report. Shortened procedure time, an acceptable morbidity (1.4%) and mortality (0.2%), and improved coronary opacification by virtue of the ease in selectively entering the coronary ostia make these preformed catheters a useful modification to coronary angiography by the transbrachial approach.


Pericardiocentesis: insertion of a pericardial catheter.

Pericardiocentesis is a lifesaving procedure in cardiac tamponade but is associated with significant and often life threatening complications. A patient is described in whom a catheter was inserted into the pericardium. This provided for prolonged pericardial drainage of purulent fluid and has the potential for decreasing the risk of this procedure.


Tricuspid whoop.

The present report describes a patient with a whooping murmur secondary to tricuspid insufficiency. The main features of this tricuspid whoop were as follows: variable in time, moving from mid to late systole; unpredictably associated with normal respiratory phases; after deep inspiratory apnea was almost constantly present.


Wegener's granulomatosis: angiographic study and case report with prolonged survival.

In the limited form of Wegener's granulomatosis pulmonary arteries were pruned and slightly stretched by a cavitating granuloma. Bronchial and renal vasculature were normal. The microscopic focal small vessel changes are not appreciable at angiography. Therefore, angiography is of no value in establishing the diagnosis of Wegener's granulomatosis.


Quantitative evaluation of coronary perfusion in man.

The usefulness and limitations of currently available techniques for quantitating coronary flow in ischemic heart disease are summarized. There are appreciable difficulties in assessing coronary flow solely from an arteriographic evaluation of the epicardial arteries. There is a considerable reserve mechanism for vasodilation at the arteriolar level, and a proximal occlusive lesion produces a reduction in flow only after this distal reserve has been exhausted. In addition, small increments in the severity of established lesions sometimes cause profound reductions in flow. The development of clinically useful flow measurements has been impeded by methodological problems related to nonuniformity of flow within the left ventricle in coronary artery disease. Validation of specific techniques for abnormal situations is difficult but possible and should probably be a prerequisite to the clinical application of any technique. When a methodologically appropriate technique is employed, average left ventricular flow per unit weight is found to be reduced systematically at rest in patients with double- and triple-vessel disease. This reduction is a group difference, however, and is not always evident in individual patients. Accordingly, more recent measurements have concentrated on the assessment of regional perfusion, and two general approaches, selective venous sampling and selective precordial sampling are illustrated. While only preliminary measurements of regional flow are available, it is clear that these measurements offer a more sensitive tool for detecting abnormalities of flow in individual patients and thereby for contributing to the management of specific clinical problems. Measurements of regional flow need to be performed during stress as well as at rest. For the future, there is also need for techniques which can assess transmural variations of flow in man and relate measurements of regional flow to regional oxygen demand. Because of the complexity of current techniques which are methodologically adequate, measurements of coronary flow will, for the immediate future, probably remain confined to clinical centers which have a special interest in them. The effort in these centers will hopefully include significant emphasis on the refinement of existing techniques so that they are more widely applicable.


Origin of the sinoatrial node and atrioventricular node arteries in right, mixed, and left inferior emphasis systems.

The origin of the sinoatrial node artery (SAN) and atrioventricular node artery (AVN) was determined for 118 patients with normal coronary arteriograms. The coronary arteriograms of the 118 patients were divided into right (66.1%), mixed (26.3%), and left (7.6%) inferior emphasis systems. The SAN arose from the right coronary artery in 53%, the left coronary artery in 35%, and had a dual origin in 11%. The proximal right coronary artery was the origin of the SAN in 48.7% of right, 60.5% of mixed, and 55.6% of left inferior emphasis systems. The left coronary artery was the origin of the SAN in 38.5% of right, 25.8% of mixed, and 44.4% of left inferior emphasis systems. The AVN arose from the right coronary artery in 84%, the left coronary artery in 8%, and from both in 8% of the 118 patients. The right coronary artery was the origin of the AVN in 98.7% of right, 74.2% of mixed, and 0% of left inferior emphasis systems. The left coronary artery was the origin of the AVN in 0% of right, 25.8% of mixed, and 100% of left inferior emphasis systems.


Treadmill exercise testing in the presence of digitals therapy or nonspecific ST-T changes: correlation with coronary angiography.

Treadmill exercise test results were studied in 93 patients with chest pain who had received digitalis therapy or had nonspecific ST-T changes in the resting electrocardiogram. Results of the treadmill test were correlated with the findings of coronary angiography. A positive treadmill result was defined as horizontal or down-sloping ST segment depression greater than or equal to 1.0 mm. Of the 40 patients with no or insignificant coronary artery disease, 15 had taken digitalis; 4 of the 15 demonstrated a positive response on the treadmill test. Of the 53 patients with coronary artery disease, 21 had taken digitalis; 15 of the 21 displayed a positive response. Among the remaining 32 not on digitalis, 20 had a positive response. The specificity of the treadmill exercise test was 96% in patients with coronary artery disease not on digitalis and whose resting electrocardiogram showed nonspecific ST changes. The specificity of the treadmill test in patients who had received digitalis was 73%. Sensitivity was 63% and 71%, respectively. By utilizing more stringent criteria in the interpretation of the treadmill exercise test (greater than or equal to 1.5 mm ST depression), among the patients on digitalis only 6.7% (1/15) with normal coronary arteries and 48% (10/21) with coronary artery disease had a positive response. With the use of the latter criterion the test was specific in 93% (14/15) of the patients and is usually indicative of coronary artery disease.


Left ventricular pressure responses in post-angiographic angina.

Alterations in left ventricular end-diastolic pressure and in dp/dt observed in ten patients with coronary heart disease who developed angina pectoris following left ventricular cineangiography were compared with those of six other patients who developed angina spontaneously and with patients who underwent left ventricular cineangiography without experiencing angina. In the patients with post-angiographic angina there was a greater increase in end-diastolic pressure than that seen in the other patients, but there was no significant change in dp/dt. Changes in left ventricular pressure associated with post-angiographic angina would appear to reflect the combined effects of increased preload provided by the contrast material and of ventricular dysfunction including diminished compliance associated with angina. A rise in end-diastolic pressure greater than 20 mmHg following left ventricular cineangiography should alert the physician that the patient may be having myocardial ischemia.


The echocardiographic diagnosis of "concealed" tricuspid stenosis.

A case is presented of a 42-yr old woman with rheumatic heart disease in whom cardiac catheterization revealed severe mitral stenosis and a low cardiac output, but no gradient across the tricuspid valve. Echocardiography clearly demonstrated the presence of tricuspid stenosis and the valve was found to be severely stenotic at surgery. This establishes the value of echocardiography in detecting tricuspid stenosis and suggests that, in some cases, it may be more sensitive than cardiac catherization in detecting this lesion.


Serial coronary arteriography with 105mm photofluorography: 24-month experience, 2,200 patients.

A 105 mm camera has been used for over 24 mo in evaluation of the coronary circulation for the most part and occasionally the proximal peripheral arteries in 2,200 patients. This photofluorographic technique provides sufficient diagnostic image detail with improved operating convenience and reduced radiation exposure compared to the large film changer. 105 mm serialography is a good adjunct to cine arteriography as a complementary film recording system, and in many cases may supplement large film serialography.


Follow-up at 11 years of children who had marked speech defects at 7 years.

The results of a follow-up study at 11 years of 215 children in the National Child Development Study who were reported to show marked speech defects at 7 years are presented. Information regarding social welfare, health and scholastic attainments was available for 190 children (88%). Over a third of these had been formally 'ascertained' for special educational treatment. Of the 124 children remaining in ordinary schools, 56% still had residual speech problems while 44% were reported to have acquired satisfactory speech. The health and scholastic attainments of these two groups are described and discussed in relation to each other and to controls. A note regarding significant items in the original reports of 25 'missing' children at 7 years is provided, indicating that the large proportion had serious additional handicaps at 7 years. The importance of effective identification, full paediatric and educational assessment and the provision of appropriate help at or preferably before school entry is stressed.


The end of mentally handicapped childhood: problems of residential transfer and school leaving during adolescence.

The evolution of two hospital units for mentally handicapped children is contrasted with two special boarding schools which each have radically different discharge procedures at adolescence. Two communities organized so as to obviate the need for adolescent transfer are discussed. Problems at adolescence highlight the interdependence of educational and social services for the handicapped. It is shown how isolated developments in residential provision may create as many problems as they are intended to solve. The difficulty of reconciling expediency with educational and humanitarian aims is discussed.


The incidence of visual handicap in Swedish children.

A sample of 1271 visually handicapped children has been analysed with regard to the degree and cause of visual impairment.


Incidence of visual defects in Yugoslavia.

1645 children of 1-7 years of age and 103 4-year-old children of an unselected population were examined. Vision screening was performed as single E optotype. Schiascopy and fixation with visuscope were also performed. Results are presented in six tables.


The prevalence of visual handicap in children in England and Wales.

An analysis of the incidence of blindness in children in England and Wales is presented, and the factors influencing registration are discussed.


Comparative value of pyruvate determination after glucose loading and transketolase determination for the diagnosis of the Wernicke-Korsakow syndrome.

The determination of transketolase activity and of pyruvic acid after glucose loading in 20 patients with the Wernicke-Korsakow syndrome and in 14 other patients is described. Glucose loading took place after the first injection of thiamine. Normal values for transketolase were found in 10 patients with the Wernicke-Korsakow syndrome, for pyruvic acid after glucose loading in three, for both of these determinations in only one patient. The normal values found for transketolase were probably due in most cases to the administration of thiamine before admission. For practical purposes it is suggested that both determinations be done in all patients with the clinical diagnosis Wernicke-Korsakow's syndrome.


Facial thermography in the diagnosis of cerebrovascular disease and in evaluation of carotid endarterectomy.

Some 60% of strokes are due to extracranial occlusive arterial lesions, most frequently at the bifurcation of the common carotid artery. Since these lesions are accessible to endarterectomy, their prestroke diagnosis is very important. Facial thermography quickly supplies reliqble information on the circulatory area in which these lesions occur, and this information can be atraumatically obtained in an out-patient setting. The success rate of facial thermography versus aortic arch angiography was 83% and 80%, respectively, in our case material, and this rate corresponds with data in the literature. In a series of 23 patients with facial thermograms and angiograms obtained before and after endarterectomy, facial thermography proved to be a useful diagnostic and prognostic aid in neurological out-patient guidance after carotid endarterectomy. By virtue of its rapidity and atraumatic character, because it can be carried out by technicians and because the findings are suitable for computer data processing, facial thermography would seem to be suitable for potential stroke screening of a high-risk asymptomatic population.


Mothers and their disturbed preschool children: an intervention study.

Children who had attended a unit for disturbed preschool children were followed up and compared to a group of children whose families had turned down the offer of a place at the unit. Measures of home and school behaviour and of social stress factors operating on the family were collected. Although treated and control children were comparable on severity of symptoms on referral, treated children showed a greater reduction in reported problem behaviour at home than did controls by the time of the follow-up interview. Attendance at the unit had a limited effect on behavior at school, however. It is suggested that if a treatment for preschool children is to have broad goals including increased competence at school as well as a reduction in problem behaviour at home, then various treatment strategies should be devised to meet these different goals.


Megadolichobasilar anomaly, basilar impression and occipito-vertebral anastomosis.

The authors describe a case of a megadolichobasilar anomaly associated with basilar impression, bilateral megadolichocarotid arteries and an occipito-vertebral anastomosis. The concurrence of these anomalies lends support to the hypothesis that congenital factors play a part in the origin of the megadolichobasilar anomaly.


Accidents in the first three years of life.

This study is concerned with a group of normal children. It reports a correlation between the condition of a baby at birth, as recorded by a modified Apgar scale, and a future history of accidental injury before age three. Various other behavioural characteristics were also associated with having scored relatively poorly on the Apgar type scale; in addition, there was some evidence that the pregnancies and previous obstetric histories of the mothers of poor birth status babies had been different. Possible connections between the behavioural characteristics and a liability to accidental injury are discussed, as is the part played by the relatively poor status at birth.


Which three-year-olds attend preschool facilities?

In an epidemiological survey of a total population of three-year-old children living in a London borough, information was obtained on the behaviour, development and social characteristics of 828 children. Details were extracted from the registers of 27 preschool facilities in the borough (a residential nursery, day nurseries, play groups and nursery schools and classes) on all children attending over an 18-month period. The patterns of attendance and factors influencing attendance of about 3000 children are discussed. The comparison of children attending facilities in the original sample of 828 with the total sample shows that those children most in need are not over-represented in these preschool groups.


A clinical and neuropathological study of a patient with abrachia (congenital absence of both arms).

This paper presents the life history and clinical history of a male patient with abrachia (congenital absence of both arms), who died at the age of 67 as a result of compression of the thoracic spinal cord caused by gibbus formation. Neuropathological examination of the spinal cord revealed unusual changes in the cervical and high-thoracic cord segments: accumulations of ependymal cells, strikingly few motor anterior horn cells and a chaotic arrangement of cell systems, along with complete absence of the cervical intumescence. These findings prompted some embryological considerations.


Urinary excretion of monoamines and their metabolites in patients with Parkinson's disease. Response to long-term treatment with levodopa alone or in combination with a dopa decarboxylase inhibitor and clinical correlations.

Urinary excretion of DA, DOPAC, 3-MT, HVA, NMA, MA, VMA and 5-HIAA were studied in 33 parkinsonian patients treated with 1.5-7.5 g of levodopa daily for up to six months and in 30 patients receiving levodopa (800-1,000 mg) combined with a dopa decarboxylase inhibitor, benserazide (200-250 mg). Basal urinary excretions were within normal limits except for that of 3-MT which was significantly lower in parkinsonian patients as compared to controls. Levodopa induced an increase of about 400 fold in urinary DA; DOPAC was increased about 300 fold, 3-MT only about 70 fold, but HVA about 300 fold. Urinary NMA and MA did not change but VMA was increased significantly. On the other hand, urinary 5-HIAA was significantly decreased. The amounts of excreted DA and its subsequent metabolities were increased with the continuation of treatment, suggesting inductive phenomena in enzyme systems. During combined treatment with levodopa and benserazide urinary DA was increased, but only to about one tenth the extent seen with levodopa alone. The excretion of DOPAC was about one 20th, of 3-MT about one fourth and of HVA one 25th that seen during levodopa treatment. No signs of enzyme induction were seen. NMA was lowered significantly but MA remained unchanged. VMA was increased and significantly more than during therapy with levodopa alone. 5-HIAA was again significantly decreased and the decrease was significantly greater than that seen with levodopa alone. Some statistically significant correlations were seen between the excretions of NMA, MA and VMA and cardiovascular side effects, indicating an affection on the NA-ergic system by levodopa treatment. Significant correlation between 5-HIAA excretion and clinical improvement of tremor during levodopa treatment may suggest that participation of 5-HT in the mechanism of tremor.


The angioarchitecture of the astroblastoma.

The angioarchitecture of an astroblastoma of the corpus collosum is studied on serial carotid angiograms, made during life, and on post mortem angiograms, performed by filling of the cerebral arterial system with a colloidal bariumsulphate solution and by using the translucidation technique. The results of these investigations are compared to the histological aspect of the tumour. This study reveals the close relationship between the astroblasts and the bloodvessels. The angioarchitectural pattern of this tumour is characterized by new formation of capillaries. It is considered as an additional support to classify the astroblastoma as a separate type of glioma.


Arsenic poisoning in childhood. An unusual case report with special notes on therapy with penicillamine.

An unusual care of arsenic ingestion involving five children is reported, which involved the process of sublimation. As2O3 was inadvertently heated in a charcoal barbecue, and the meat cooked thereon was contaminated. It is possible that the sublimation may have potentiated the toxicity of the usually mildly toxic, relatively unsoluble As2O3. Penicillamine was used in the latter part of the therapy in three cases after initial dimercaprol, and the clinical effect of penicillamine was particularly dramatic in one case in which dimercaprol discontinuation had been accompanied by recurrent symptoms. Remarks on the mode of action of penicillamine are made. More work needs to be done to establish the possible role of penicillamine in arsenic poisoning.


Taste as a deterrent in pediatric poisonings.

Seven hundred and two children were tested to see how much they would ingest of two commercially available potassium supplements, one an effervescent tablet and the other a powder. The results showed that the children would not ingest either formulation in amounts that even equalled a single adult therapeutic dose. The children appeared to be deterred by both the effervescent quality of the tablet and the unpleasant, metallic after-taste of the powder. An unpleasant taste may act as a deterrent to the child, keeping him from ingesting a toxic amount of a product, at least, when the product has relatively low toxicity.


A rapid and precise method for determining theophylline in serum.

We report a spectrophotometric method for determining theophylline that is useful as a routine method for monitoring serum theophylline concentrations. The recovery of theophylline from serum is essentially 100% whem compared with aqueous standards taken through the entire procedure. Barbiturates, which interfere with most ultraviolet spectrometric methods for theophylline, do not interfere with this method. The procedure requires less than 45 min for completion and is more sensitive than most spectrophotometric methods for determining theophylline.


Granulomatous arteritis.

Granulomatous, or temporal, arteritis is a disease of older people and should be considered when any patient over 55 years old has complaints consistent with a multi-system disease and/or visual loss, especially if combined with a history of diplopia, amaurosis fugax, loss of vision, or with the findings of ischemic optic neuritis or central retinal artery occlusion. Treatment should be instituted immediately with high doses of corticosteroids. The sine qua non for the diagnosis is a positive temporal artery biopsy when ocular involvement is a feature of the disease. Treatment includes administration of systemic and retrobulbar steroids. The ESR is used as a guide in determining the level of maintenance steroid dosage.


Chronic obstructive pulmonary disease.

The diagnosis of COPD can easily be made on the basis of history, physical findings, and simple laboratory procedures. Treatment is aimed at symptoms and is individualized to the patient's needs. Therapy must be given on a long-term basis. The patient should be educated in the basic nature of his disease and encouraged to return to as normal a life as possible. Patients with COPD often are severely restricted in their earning ability, and treatment can cause a severe financial drain. Thus the physician should carefully consider costs--especially the cost of medications. Finally, the correct choice and use of the many therapeutic measures available can yield marked symptomatic relief and improvement in lifestyle--often allowing the patient to return to productive employment.


Transient ischemic attacks.

The treatment of TIA must be individualized. TIA is one of several manifestations of generalized atherosclerosis. While one-third of patients with TIA will suffer a stroke in five years, one-half of the same group will die of myocardial infarction. The risk of stroke is greater in carotid rather than vertebral-basilar TIA, in older patients, and in those with a cluster of TIAS, an is highest in the first month after the TIA. Treatment should reflect this knowledge.


Stress and distress.

I must ask the reader's indulgence for this article's concern with applications of the stress concept, which are distinct from, although related to clinical medicine. It has not been my object to deal with the way physicians have been aided by stress research in the practice of medicine--that information is already widely available. Rather, I have attempted to sketch briefly the history of the stress theory and to demonstrate how this information can help anyone, physician or layman, lead a more complete and satisfying life. The applications of the stress theory have been dealt with at length elsewhere. I believe that we can find within scientifically verified observations the basis of a code of behavior suited to our century. The great laws of nature that regulate the defenses of living beings against stress of any kind are essentially the same at all levels of life, from individual cells to entire complex human organisms and societies. It helps a great deal to understand the fundamental advantages and disadvantages of catatoxic and syntoxic attitudes by studying the biologic basis of self-preservation as reflected in syntoxic and catatoxic chemical mechanisms. When applied to everyday problems, this understanding should lead to choices most likely to provide us the pleasant eustress (from the Greek eu meaning good, as in euphoria) involved in achieving fulfillment and victory, thereby avoiding the self-destructive distress of frustration and failure. So the translation of the laws governing resistance of cells and organs to a code of behavior comes down to three basic precepts: 1. Find your own natural stress level. People differ with regard to the amount and kind of work they consider worth doing to meet the exigencies of daily life and to assure their future security and happiness. In this respect, all of us are influenced by hereditary predispositions and the expectations of our society. Only through planned self-analysis can we establish what we really want; too many people suffer all their lives because they are too conservative to risk a radical change by breaking with hiabits or traditions. 2. Altruistic egoism. The selfish (i.e., self-interested) hoarding of the goodwill, respect, esteem, support, and love of our neighbors is the most efficient way to give vent to our pent-up energy and to create a more enjoyable, beautiful, or useful environment.3. Earn thy neighbor's love. This motto--which is merely a rewording of the command to "love thy neighbor as thyself"--is compatible with man's natural structure, and although it is based on altruistic egoism, it could hardly be attacked as unethical. Who would blame the man who wants to assure his own homeostasis and happiness only by accumulating the treasure of other poeple's benevolence and love? Yet this makes him virtually unassailable, for nobody wants to attack and destroy those upon whom he depends.


Hand preference and the laterality of cerebral speech.

A theory of the origins of hand preferences (Annett, 1972) is outlined and its implications for the distribution of cerebral speech in handedness groups are examined. Five studies of dysphasia in right and left handers with unilateral cerebral lesions are compared and found surprisingly consistent. Data from three series found alike in all essential respects are combined to give a substantial number of cases with which to test the expectations of the theory. The agreement is close enough to justify a reconsideration of the model in the light of the evidence and also an analysis of possible reasons for the main differences between series. In spite of the many uncertainties involved in inferences from dysphasia to cerebral speech laterality, it is concluded that the evidence is strong enough to offer a useful test of hypotheses as to the distribution of cerebral speech in handedness groups. Other questions bearing on handedness and cerebral speech are briefly considered in order to show the explanatory range and power of the theory.


Long and short term memory in head injured patients.

A group of severely head injured patients were compared with 15 controls on auditory vocal digit span, and on a free recall memory task, enabling short term memory (STM) and long term memory (LTM) to be examined. The free recall curves differed for the two groups suggesting that the head injured patients had an essentially normal STM, but a poor LTM. This was supported by the finding of a significantly lower number of semantic errors (presumably retrieved from LTM) and a normal digit span (STM) in the head injury patients. The severity of the injury as judged by post-traumatic amnesia or the presence of neurological signs at the time of memory testing showed only a weak relationship to the severity of the memory deficit. The presence of a skull fracture was of minor importance in determining the severity of the LTM defect. Patients tested early after the injury were significantly poorer on STM, but not on LTM.


Verbal and non-verbal short-term memory impairment following hemispheric damage.

Short-term memory was investigated in 30 control and 125 unilaterally brain-damaged patients with a series of tests requiring the immediate reproduction of strings of items of increasing length. In three tests the items were auditorially presented digits or words: one test asked for oral repetition of digits, while the other two required the patient to point to written digits or to pictures. The fourth test aimed at measuring spatial span. On both the Digits Forward test and the two other verbal tests not requiring the use of speech, left brain-damaged patients were impaired in comparison to normals, while the right brain-damaged patients were not. Aphasics had a significantly shorter verbal span than non-aphasic patients with left hemisphere damage. Spatial span, on the other hand, was significantly affected by a lesion posteriorly located in either hemisphere, but not by aphasia. Two patients with an exceedingly poor verbal memory span were observed, one suffering from anomic aphasia and the other from conduction aphasia. There were also two right hemisphere damaged patients who showed an extreme reduction of spatial span, which could not be accounted for by space perceptual disorders and contrasted with a normal performance on a spatial long-term memory test.


Simple reaction-times to speech and non-speech stimuli.

Two experiments were carried out involving the measurement of simple reaction-time when subjects responded to speech and to non-speech stimuli. In the first, subjects were required to make a speech response (uttering the vowel [a: ]) to one speech stimulus (the vowel [a: ]) and three non-speech stimuli (a complex tone, a telephone bell and a click). The click stimulus gave significantly longer reaction-times than the other three stimuli; since all stimuli were equated for peak intensity delivered to the subjects' ears, this was due to the short duration of the click (25 msec). There was no evidence that compatibility between the speech stimulus and the speech response had any influence on reaction-time. The second experiment employed a 2 X 2 design with 2 stimuli and 2 response modes. The stimuli were the vowel [a: ] and the telephone bell; the response modes were key-pressing and uttering the vowel [a: ]. The speech stimulus and the speech response gave significantly longer reaction-times than the non-speech simtulus and response. The minimum time for a reaction requiring speech reception is of the order of 180 msec. and the use of the motor speech mechanism adds about 30 msec. to reaction-time. Again no interaction was found between stimulus and response and this is probably due to the extremely simple nature of the speech tasks imposed.


Dyslexic adolescents: evidence of impaired visual and auditory language processing associated with normal lateralization and visual responsivity.

The questions of whether chronically dyslexic adolescent suffer any deficits of simple language stimulus processing or are less left hemisphere dominant than normal reading controls were addressed. The dyslexics were chosen for clarity of their specific reading problem and were older than dyslexics previously studied with lateralizing tests. Tasks administered in Experiment I were unilateral and bilateral tachistoscopic work recognitions and a tachistoscopic recognition report-time task for single lateralized letter stimuli. Experiment II, conducted a year later, readministered these tasks with modifications, and added dichotic digits and motor reaction time-stimulus detection tasks. It was concluded that right handed, chronic dyslexics: (1) possess left hemisphere language specialization; (2) show normal interhemispheric processing delays for single letter stimuli; (3) are, unlike nondyslexis but equally poor-reading Ss, clearly impaired in their efficiency of visual and auditory processing of simple language stimuli; (4) possess clear auditory memory deficits for verbal material; and (5) may possess an additional deficit of left hemisphere visual association area function.


Implicit processing of grammatical rules in a classical case of agrammatism.

The speech production of an agrammatic patient is viewed as the output of a syntactic filter which allows only nouns, verbs, and adjectives to pass. In this paper, we study the behavior of this filter in the processing of grammatically ambiguous words. Our results indicate that these words are either uttered or not as a function of their syntactic role in the sentence. Thus, the patient's oral reading of a sentence is not a concatenation of isolated words, but depends on an implicit, context-sensitive analysis. These observations bring to light a new aspect of the agrammatic's syntactic competence and may contribute to the study of psycholinguistic processes in normals.


Stuttering repetitions in aphasic and nonaphasic brain damaged adults.

Stuttering repetitions were analyzed by frequency of occurrence in aphasic and nonaphasic brain damaged adults. Aphasics used significantly more stuttering repetitions than did nonaphasics. The frequency distribution of stuttering repetitions among aphasic subgroups indicated a relationship with sound problems in anterior and posterior groups.


Auditory modality-specific anomia: evidence from a case of pure word deafness.

In a patient with a classical syndrome of pure word deafness following a cerebrovascular accident detailed neuropsychological examination showed an almost absolute inability to name meaningful non verbal sounds, in spite of normal recognition as demonstrated by ability to match the sound with the corresponding natural source. This selective anomia, confined to auditory modality, is discussed in view of the previous researches regarding the general field in naming disturbances, which showed that for the vaste majority of aphasics, anomia was not modality dependent. Besides that the contrasting performance of the patient who showed complete lack of phonemic analysis matched with normal recognition of some acoustic parameters of speech as prosody and stress is discussed.


Variegated translocation mosaicism in human skin fibroblast cultures.

The term "variegated translocation mosaicism" is used to describe the repeated occurrence, within cultures of human skin fibroblasts, of a multiplicity of chromosomal rearrangements. With respect to the frequencies of such cytogenetically aberrant clones we found that they (1) were not detectable in routine diagnostic skin fibroblast cultures from 29 subjects with a wide variety of indications for biopsy; (2) were not detectable during in vitro aging of diploid strains with four normal individuals; (3) could be detected after rescue from bacterial contamination of a culture from an otherwise normal diploid male; (4) occurred with high frequencies in independent cultures from another apparently normal subject; (5) occurred with high frequencies in multiple biopsies obtained at autopsy from a patient with Werner's syndrome who died of sepsis; (6) were of pseudodiploid nature; and (7) involved a different spectrum of chromosomes in different individuals. A consistent association with mycoplasma contamination could not be made.


Confirmation of the synteny of the human genes for mannose phosphate isomerase and pyruvate kinase and of their assignment to chromosome 15.

The synteny of human mannose phosphate isomerase and pyruvate kinase and the assignment of the genes for these two enzymes to chromosome 15 were confirmed by analysis of 43 independently derived human-mouse hybrid clones. Hybrids between mouse cells deficient in hypoxanthine-guanine phosphoribosyltransferase and human fibroblasts carrying an X/15 chromosome translocation were also included in this study.


The interrelationships of chromosome banding patterns in procyonids, viverrids, and felids.

The Giemsa banding patterns of the chromosomes of 4 species of Procyonidae, 13 of Viverridae, and 6 of Felidae have been studied. The patterns have all been related to the basic felid karyotype. Each procyonid and viverrid has a distinctive karyotype, whereas some felids have indistinguishable karyotypes even when banded. Extensive interfamilial G-banding conservatism has been demonstrated, with many chromosomes being "shared" by all three families. A chromosome identification and karyotyping system for the Carnivora has been devised to facilitate comparison of data from future studies. Phylogenetic implications of the findings have been discussed.


Cytogenetic investigations in families with ataxia-telangiectasia.

Chromosomal studies were performed on peripheral blood lymphocytes and cultured skin fibroblasts from five Israeli-Moroccan families with ataxia-telangiectasia. A total of 24 individuals, including seven propositi, was investigated. Among the probands, significantly elevated rates of chromosome damage were observed in both blood and skin. Skin fibroblasts of affected individuals showed several orders of magnitude more chromosome breakage than lymphocytes. Increased rates of chromosome damage were also observed in the fibroblasts of some phenotypically normal family members (obligate heterozygotes and sibs) when compared to normal controls. An apparent abnormal clone of cells, possessing a large acrocentric marker chromosome (14q+), was observed in varying proportions among cells of all the propositi (2-5% of lymphocytes; 1-9% of fibroblasts).


The objective and timing of drug disposition studies, appendix I. Species differences in the tissue distribution of metazimid, an imidazolone derivative.

A marked species difference has been observed in the tissue distribution of metazimid in the rat vs the dog after repeated doses. Differences in toxicity between these species are consistent with tissue levels but not plasma levels. No species differences in patterns of drug metabolism could be found in association with the marked difference in tissue cumulation.


The objective and timing of drug disposition studies, appendix II. Plasma concentrations of oxyphenbutazone in dogs given oxyphenbutazone or the calcium or sodium salts of its phosphate ester.

Plasma levels of oxyphenbutazone were measured in beagle dogs following oral administration of oxyphenbutazone and salts of oxyphenbutazone phosphate. Dosage with sodium and calcium salts of oxyphenbutazone phosphate produced higher oxyphenbutazone plasma levels than dosage with oxyphenbutazone itself. Oxyphenbutazone phosphate was not detected in plasma following oral dosing with salts of oxyphenbutazone phosphate but was found in plasma following intramuscular administration of oxyphenbutazone phosphate sodium salt. A metabolite, oxyphenbutazone glucuronide, was found in plasma of dogs following administration of either oxyphenbutazone or salts of oxyphenbutazone phosphate.


An economic principle for regulating rhythms of plants.

Supposing that rhythms as biological events must be teleologically regulated, the phase relations of the rhythms in the leaf movement of Canavalia ensiformis, exposed to periodical light-darkness changes, are investigated. Pergressive Fourier analysis is applied because it is especially suitable for such analyses. In order to understand the demonstration, a short description of this method is given. It is a variant of the Schuster method, developing at the end of the last century. It is demonstrated in particular that the three parameters of a sine function can be calculated. The key for this calculation is a parallel effect in the phase diagram by which it is possible to calculate the period T of a sine even if the analysis interval p is not a whole-numbered multiple of the period T. Because this parallel effect occurs even if the parameters of a sine have more or less great random oscillations, a heuristic principle is defined for revealing sine-like rhythms hidden in a curve or data. Its approximation to the analyzed curve or data can be calculated by an application of the method of the error squares of Gauss or by drawing. By applying this method it is demonstrated that the leaf movement of Canavalia ensiformis follows an economic principle if the plant is exposed to artificial changes of light and darkness of different periods. The rhythm with the weaker amplitude is so regulated by the stronger rhythm that extreme values coincide as much as possible. By such movement of the leaves the plant applies the smallest amount of mechanical energy, to produce the weaker rhythm simultaneously with the stronger.


The switch mechanism in periodic catatonia and manic-depressive disorder.

Both in periodic catatonia and in manic-depressive disorders sudden switches occur in behavior, in the autonomic nervous system and in the catecholamine metabolism during the transition from interval or depression into catatonia or mania. Both the manic and the catatonic attacks seem to be superimposed on the basic depressive or schizophrenic illnesses. The attacks can be counteracted or suppressed by psychotropic drugs such as alpha-methyldopa, disulfiram, reserpine, haloperidol or chloropromazine which interfere with the catecholamine metabolism or their receptor sites. The involvement of the catecholamines may however be secondary to primary defects in the thyroid, the hypothalamus or the limbic system. The strict periodicity in periodic catatonia points to an accumulation of some active metabolite which may be produced centrally during the interval. At a certain level it may trigger the switch-mechanism and then be reduced during the catatonic phase. In periodic catatonia both the basic schizophrenic disease as well as the periodic manifestations are compensated by thyroxine-thyroid treatment.


The objective and timing of drug disposition studies, appendix III. Diethylpropion and its metabolites in the blood plasma of the human after subcutaneous and oral administration.

Diethylpropion hydrochloride is an effective anorexiant at the recommended dose of 25 mg three times a day. Previous work in volunteers to evaluate the effects of much larger doses showed that 400 mg given orally was equipotent with 600 mg subcutaneously in terms of subjective and physiologic effects, i.e., the drug was more potent orally than subcutaneously. In one volunteer, blood level studies after a 600-mg subcutaneous dose showed concentrations of unchanged diethylpropion in the plasma about three times as high as those found after the equipotent 400 mg oral dose. In nine other volunteers, the plasma concentrations of unchanged diethylpropion found after a 75-mg oral dose was less than 1/100 of that observed after a 400-mg oral dose. These observations suggest a rapid but limited metabolic capacity for conversion of diethylpropion to its metabolites. The data indicate that the metabolites, rather than the parent drug, are responsible for the pharmacologic responses seen with doses much larger than those necessary for inducting anorexia.


The objective and timing of drug disposition studies, appendix IV. Phenylbutazone formulations: in vitro dissolution and in vivo performance.

Human plasma level studies were conducted on various phenylbutazone formulations. The resultant data indicated that the nature of the formulation had a marked influence on the rate of phenylbutazone absorption. An in vitro dissolution rate apparatus was employed in an attempt to predict potential absorption of phenylbutazone from a given formulation. Based upon the in vitro-in vivo correlation, a new phenylbutazone tablet product was developed which produced a complete and more rapid absorption of the drug.


Autorhythmometry in manic-depressives.

Three manic-depressives were studied longitudinally. Several times a day, the patients measured and recorded their mood, vigor, oral temperature, finger counting, blood pressure, pulse rate, and urine volume. Then the acrophases of their circadian rhythms were computed by a least-squares fit. These patients displayed rhythm phases that were grossly abnormal. Systematic acrophase changes over time supported the hypothesis that manic-depressives have circadian rhythms that free-run faster than one cycle per 24 hrs. Lithium appeared to slow these rhythms and help the environmental synchronizer force physiological functions to coordinate better with the usual 24-h environmental cycles.


Circadian rhythms of electrolyte and 17-hydroxycorticosteroid excretion in hyperthyroidism and hypothyroidism.

The circadian rhythms of excretion of sodium, potassium, calcium, magnesium, phosphorus and 17-hydroxycorticosteroid (17-ohcs) were determined in five normal subjects, in six patients with hyperthyroidism and five with hypothyroidism. Constant diets with identical 3-hourly feedings were employed, and urine collections were made every 3 hrs during a 3-day study period. The circadian patterns of urinary excretion of sodium, potassium and 17-OHCS were similar in all three groups with distinct daytime peaks and nighttime nadirs. The total quantities of the ions and 17-OHCS excreted were greater in hyperthyroid than in hypothyroid patients with the greatest difference noted with the 17-OHCS. The rhythms for calcium, magnesium and phosphorus excretion were accentuated in hyperthyroid patients but similar to those in normal subjects with early morning calcium and magnesium peaks and a phosphorus peak approximately 12 hrs later. While a similar although blunted circadian pattern for calcium and perhaps magnesium excretion was noted in hypothyroid patients, their phosphorus rhythms were distorted and rather flat. These latter results confirm the observation of MINTZ et al. and are compatible with their interpretation that thyroid hormone is permissibly necessary for the expression of a normal phosphaturic rhythm and that the circulating level of thyroid hormone influences the amplitude of the phosphaturic rhythm.


[Comparative studies of the glycogen content in the gingiva in patients with periodontal disease and in experimental dogs].

Comparative examinations were carried out on the Glycogen content in the gingiva of patients suffering from parodontal disease as well as in dogs with experimental model of parodontal disease. The latter was obtained by stimulation of the mandibular nerve by means of a silk ligature. Thirty-five biopsies were taken from the patients, suffering from parodontal disease and eight - from 4 experimental dogs. The preparations were treated with periodic acid (PAS reaction).


[Studies of the changes in the content of total serum protein and protein fractions of white Wistar laboratory rats in the process of ontogeny].

The authors examined the changes in the content of the total protein and the protein fractions during the process of Ontogeny in the Blood Serum of 10 female and 10 male random bred rats of the Wistar strain. The examinations were carried out on the fifteenth, thirtieth, sixtieth day of age and when the rats were one year old. The authors found that the content of the total protein in the blood serum in both sexes was increased with advancement of age alpha2-, beta- and gamma-globulin fractions showed a tendency to an increase with advancement of age. The fraction albumin + alpha1 globulin was diminished quantitatively with advancement of age in both sexes.


[Reaction to injury and recovery in the arterial wall].

The author describes the histological and ultrastructural manifestations of the reactions of the arterial wall after experimental damage and the phases, through which the process of repair passed. After the initial response the standard hemostatic and inflammatory reaction in all cases occurred substitution of the damaged areas of the arterial wall and regeneration of the involved cellular components of the arterial tissue, which caused repair of its integrity. The repair reaction was manifested with proliferation of smooth muscle cells in the subendothelial area of the damaged artery and with abundant accumulation of the connective tissue martrix, which after some period of time caused formation of the so called intimal thickening. In cases with many massive intimal thickenings there were disturbances in the transparietal diffusion of oxygen and nutritive substances, which affected favourably the penetration of serum lipoproteins in the arterial wall and facilated for the development of atherosclerosis in the zones of the preceding arterial damage.


[Studies on the differences between the skin of nude mice and bald skin in man].

The author carried out studies and established that in contrast to the bald skin of a man the elastic fibres in the skin of naked mice were completely normal and the small arteries and arterioles were with normal structure, because of which they could not be considered as a cause of degeneration of hair follicles, falling of hairs and of their irreplaceability with hairs grown externaly in these animals (fig. 4 a and b, fig. 5 a and b). The processes, occuring in the skin of the mice, are determined genetically and their manifestations represent changes in features, which, induced by mutation, are inherited.


[Distribution of methionine-75Se in animals with experimental atherosclerosis treated with a protein hydrolysate].

It is well known that accumulation of methionine in the internal organs is weaker in animals with experimental atherosclerosis. On the basis of this concept the authors carried out studies on rabbits and guinea pigs with atherosclerosis, induced by cholesterol diet and treated with protein hydrolysate-hydropront in a dose of 5 ml/kg of body weight daily for rabbits and every two days for guinea pigs. Distribution of methionine 75Se was examined in the internal organs. The radioisotope in a dose of 5 microcurie was injected two hours before killing of the animals. There was a reduced accumulation of methionine 75Se in the internal organs of rabbits and guinea pigs with experimental atherosclerosis. The disturbances were increased after prolongation of cholesterol feeding. The application of protein hydrolysate considerably improved the accumulation of methionine in the treated animals compared with the untreated animals with atherosclerosis.


[Changes in kidney function and the cortisol and ADH levels after peritoneal dialysis with 5% glucose in dogs].

The authors made peritoneal dialisis with 5% of glucose (7 ml/kg of body weight) in 11 dogs under the conditions of an acute experiments. They examined cortiosl and ADH activity, hematocrite and plasma protein in the samples of blood, obtained on the 20th and 50th minute. ADH was titrated biologicaly by a new method, proposed by Nacev. The results were compared with the changes in the circulatory and renal indices, obtained at the same procedure in the preceding investigations. There was an increase in the cortisol and ADH activity, which could be explained by the total hypovolemia, induced by peritoneal dialisis. The increase of the cortisol level is described as a separate link in a more complex mechanism, assuring metabolic homeostasis.


[Autoradiographic study of liver regeneration after treatment with carbon tetrachloride and heterologous antihepatic serum].

The authors carried out an autoradiographic study on the regeneratory processes in liver of 130 rats, which were treated with carbon tetrachloride and heterologous antiliver serum at various dilutions. The obtained results showed that this serum stimulated the synthesis of DNA in the parenchymal mesenchymal cells of liver, damaged diffusely. The effect of stimulation on DNA-synthesis in the animals of the experimental group, treated with 0,5 ml of heterolougous antiliver serum in dilution of 1:10 with saline, was mostly manifested. According to the authors the stimulation of DNA-synthesis was accomplished most probably by means of the mechanisms of the so called "immune enhancement".


[Standardized system for incorporating labelled amino acid in vitro with rat spleen fractions].

The authors describe a standardized system devoid of cells with polyribosomes and total cellular juice, obtained from a rat spleen. They discuss the dependence between incorporating capability and the temperature of incubation, concentration of magnesium ions as well as the significance of single components for the optimal capacity of the incorporating system.


[Terminal bundle-branch block (TBB) in acute and chronic overloading of the right heart].

The authors performed a model loading of the right heart ventricle in 40 dogs in 17 dogs--acute tension loading by creating a partial ligature (banding) of the pulmonary artery; the dogs were examined in respect to the changes hemodynamics and ECG for a period of three hours. In the second group of 10 dogs a chronic tension loading of the right heart was created by a partial ligation of the pulmonary artery (banding); the dogs were followed--up in respect to hemodynamic and vectocardiographic changes for a period of one year. In the other group of 10 dogs a chronic loading of the right heart: was formed by operative route and interatrial defect was obtained; the dogs were followed-up in respect to hemodynamics and vectrocardiographic changes for a period of one year. The authors described the changes in the intraventricular conduction of vectro cardiograms, made by the three plane system of Akulincev, and these vectrocardiograms were compared with the type and degree of loading as well as with the morphologic changes occurred in the heart. The authors indicated the nonspecificity of TBB as a sign of volume loading of the right heart ventricle.


[Spasmolytic activity of a piperazine derivative under the code number of 4P-79].

The author examined the pharmacologic spasmolytic action of a pyperasine derivative under the code 4P-79. She examined the effect of the compound on four types of spasms, induced by acethylcholine, nicotine, histamine and serotonine on an isolated rabbit intestine. The mean effective concentrations were determined and they were compared with the mean effective concentrations of papaverine and benzylharmine, estimated in parallel experiments. It was found that 4P-79 had high spasmolytic activity, surpassing several times that of the preparations used for comparison. There was a marked antiserotonine effect on the first place. The compound was examined also on an intestine "in situ" by the method of Nikolaev Comparative experiments with papaverine and deseryl were conducted.


[Gentamicin toxicity to animals of both sexes and different ages].

Gentamycin acute toxicity in sexually-immature and sexually-mature male and female rats was tested comparatively. DL50 for the female sexually-mature rats was found to be statistically reliable lower than that for the remaining three groups of animals. The greatest differences were observed in the values for the maximum non-lethal and minimum lethal doses of this antibiotic. The authors suggeste the use of a new index for the evaluation of gentamycin acute toxicity called Dose Range Index.


[Effect of nivaline on some links in the oxidation-reduction and energy processes in striated and cardiac muscles].

The authors examined the effect of nivaline on the oxyreductive and energetic processes in the striated and smooth muscles under the conditions of a laboratory experiment. After determining the changes occurred in the succinatdehydrogenase, glutamat-dehydrogenase, glutamat-oxalacetic and glutamat-pyruvic transaminases, adenosinotriphosphate and adenosinemonophosphate, the authors found that nivaline enhanced oxyreuctive and energetic processes, connected with accumulation of adenosintriphosphate, which abolished quickly the fatique.


[Our experience with the Soviet "Thromb-2" thromboelastograph].

The soviet thrombelastograph "Thromb-2" is four-channel, recording the processes of coagulation of whole and citrate blood at 37 degrees C. It is used for macro- and micro tests as micro tests are performed with peripheral blood as well. The recording of the process is achieved immediately by means of a moving diagram paper for a two-sided or one-sided record, using writing apparatus with ink. The velocity of the diagram paper is such that it assures a great precission of the recording. The charaeter of the thrombelastogram itself is determined by an electrical signal, proportional to the elasticity of the formed blood coagulum. Maintenance of the thrombelastograph with paper and ink is easy, available and cheap.


[Excretion of dopamine, noradrenaline, adrenaline, vanilmandelic acid and 5-hydroxyindoleacetic acid in the urine of volunteers treated with adepren].

The authors examined the excretion of dopamine, noradrenaline, drenaline, vanylalmond acid and 5-hydroxyindolacetic acid in urine of healthy volunteers, treated with the original Bulgarian preparation Adepren for a period of ten days. There was an increase of the excretion of dopamine and adrenaline, but a tendency to a reduction of noradrenaline and vanylalmond acid. There were no changes in the excretion of 5-hydroxyindolacetic acid. The authors interpreted the obtained results most probably of MAO-inhibiting effect of the preparation.


[K+, H+ and Ca++ concentrations in the perivascular fluid as a factor in the regulation of the lumina of the vessels of the pia mater].

The author separed the vascular vessels of pia mater with a size of 20-150 microns in cats under penthobarbital narcosis. The perivascular area of the vessels was perfused by an artificial fluid with varying concentrations of potassium, hydrogen and calcium. The local contraction of the smooth vascular musculature was induced by stimulation  with rectangular impulses by means of electrodes introduced by micromanipulators in immediate vicinity of a vessel. The changes were recorded by means of microphotographic images of the vessels. It was established that the contraction of the vessels was observed when there was a lack of potassium or at concentration of 100 meq/l. There was no change at 2,5-3,0 and at 50-60 meq/l of potassium. Vasodilatation was found at 10-20 meq/l. Electrical stimulation caused stronger contraction of the vessel, when there was a lack of potassium in comparison with the norm (2,7 meq/l). The increase of potassium caused a reduction of the dimensions of the effect due to electrical stimulation. The vascular dilatation, induced by 10-20 meq/l of potassium was not affected by the increase of the calcium concentration (6-9 meq/l) in artificial fluid. The vasodilatation, induced by an increase of hydrogen, was abolished by raising the concentration of calcium in the artificial fluid. The obtained results were discussed.


[Normal urinary excretion of androgenic hormones in rats studied by a thin-layer chromatographic method].

The author determined the parameters of the normal excretion of androgenic hormones and their metabolites (10 separate components) in urine of male and female rats, using the method of thin-layer chromatography. The results could be accepted as norms of the androgenic excretion in white nonbred rats. Eight biological important coeffieients of androgens were found in urine of normal rats. The author discussed the physiological peculiarities of the androgenic excretion in rats. The report indicates the significance of thin-layer chromatography in determining the metabolic profile of androgens in urine of a rat in view of examining the functional state of the adrenal cortex, gonads and liver under various experimental conditions.


[Acid phosphatase and beta-glucuronidase in the peripheral blood leukocytes and in blast transformation in cell cultures stimulated with phytohemagglutinins (PHA)].

The author examined the enzymic content of lymphocytes and the changes, which occurred after stimulation with phytohemaglutinins (PHA). There was a difference in the reaction of lymphocytes in healthy persons, in patients with virus diseases and in persons with malignant lympholeucosis.


[Early effect of cortisol on the in vitro binding activity of rat spleen polyribosomes].

The authors examined the influence of cortisol during the first eight hours after its intraperitoneal administration in rats on the spleen and its polyribosomes. It was found that the weight of the spleen, referred to the body weight, diminished statisticaly significantly six hour after hormone application. The translirating activity of the polyribosomes of the spleen at the same time and this was not due to the presence of an inhibitor or to a deficit of the information RNA, but to changes in the ribosomes themselves.


Release of calcitonin by cultures of medullary carcinoma of the thyroid.

Three biopsies of medullary carcinoma of the thyroid were grown in monolayer culture. All three cultures initially released high levels of calcitonin into the medium, but the conretion from the culture cells was not stimulated when the medium calcium concentration was increased from 1.8 to 3.6 mEq/L. Four peaks of calcitonin immunoreactivity were found when the culture medium of one cell line was fractionated by gel filtration on Bio-Gel P-10. This closely corresponded to the heterogeneous molecular profile of calcitonin in the serum of this patient and other patients with medullary carcinoma of the thyroid.


The hypothalamo-pancreatic axis: evidence for a neurohormonal pathway in the control of the release of insulin and glucagon.

Segments of freshly dissected rat hypothalamic tissue corresponding to the ventrolateral (VLH) and ventromedial (VMH) regions were incubated in Gey and Gey medium at 37 C under 95% O2 and 5% CO2 for 30 minutes. Groups of male rats which had been fasted for 6 hours received injections (i.v.) of either VMH medium or VLH medium while a third group received control medium only. Blood samples were taken from the aorta 3 minutes post-injection and circulating levels of insulin and glucagon were determined by RIA. The medium from the incubation of the VMH tissue significantly elevated glucagon levels and significantly lowered plasma concentrations of insulin compared to the levels in animals receiving injections of control medium. The hormone levels in animals receiving an injection of medium in which VLH tissue had been incubated did not differ significantly from the controls. In another type of experiment VMH medium, but not VLH medium, was able to overcome the somatostatin-induced inhibition of glucagon release. These observations suggest that hypothalamic factors may be involved in the regulation of the endocrine pancreas.


Sex differences in the urinary catecholamines.

Urinary excretion of dopamine, norepinephrine and epinephrine was measured in a group of adult men and women of comparable age during recumbency and then during stimulation by upright posture. Urinary norepinephrine was found to be significantly higher in women (30.3 +/- 4.4 ng/min/m2 B.S.) than in men (18.3 +/- 2.7 ng/min/m2 B.S.) during recumbency; there was no significant sex difference in dopamine and epinephrine excretion. There was no apparent trend indicating a difference in urinary catecholamine excretion during the follicular or luteal phase of the menstrual cycle. In response to upright posture, there was a significant decrease in the urinary dopamine-norepinephrine ratio in both sexes; the magnitude of the decrease was, however, significantly higher in men (-9.9 +/- 3.0) than in women (-2.05 +/- 0.72). The mechanisms of the sex differences in urinary catecholamine excretion are unknown. Clinical studies involving catecholamines have to take these sex differences into account.


Synthetic analogues of residues 1-34 of human parathyroid hormone: influence of residue number 1 on biological potency in vitro.

A biologically active tetratriacontapeptide of human parathyroid hormone, hPTH (1-34), has been synthesized together with a series of structural analogues involving changes at the amino-terminal residue. Acetylation of the terminal amino group results in a marked reduction in the biological potency as measured in the in vitro rat renal adenylyl cyclase assay. Deletion of the terminal amino group results in a loss of biological activity. Substitution of the amino-terminal serine residue with glycine gives a lowered potency whereas substitution with alanine results in a 2-5-fold increase in biological activity in the in vitro assay. The results are compared with the findings previously reported for a series of amino-terminal analogues of the bovine PTH 1-34 peptide.


Effect of estradiol on the early incorporation of (3H) thymidine into uterine DNA on immature mouse.

The incorporation of [3H]thymidine into uterine DNA was markedly depressed within 10 to 30 minutes after intraperitoneal administration of 17beta-estradiol to immature mouse. Maximum inhibition occurred about 6 hours after the hormone was administered. Uterine DNA content and the amount of [3H]thymidine incorporated into the acid-soluble fraction was not affected during the period of hormone-induced inhibition. Moreover, the in vitro incorporation of [3H]thymidine by isolated estradiol-treated mouse uterus was blocked. In contrast to the uterus, 17beta-estradiol did not influence the incorporation of thymidine into mouse liver DNA. Evidence is presented to show that the incorporation of thymidine into uterine DNA was blocked initially by 17beta-estradiol.


[Excretion of estriol-3-sulfate in the urine of pregnant women during the last trimester of pregnancy].

In this publication a method is given for quantitative determination of estriol-3-sulfate in urine of pregnant women. After separation of estriol-3-sulfate from glucuronides by liquid partition using acetone and NaOH the sulfate is hydrolyzed to estriol. The estriol is converted to an azodye which is separated by TLC and measured by remission analysis which a chromatogramm spectrophotometer. 59 cases have been investigated and the excretion pattern is given for estriol-3-sulfate in the 3rd trimester of pregnancy. The average excretion is 100 mug/24 hours in the 28th week and 356 mug/24 hours in the 42nd week of pregnancy.


[Excretion of estriol, estetrol, 16-epi-estriol, 16-keto-estradiol and 16-hydroxyestrone in the 24-hour urine of pregnant women in the last trimester].

In this publication a method is given which allows simultaneous estimation of estriol, estetrol, 16-epiestriol, 16-ketoestradiol and 16-hydroxyestrone in urine of pregnant women. First conjugates are precipitated with ammoniumsulfate and hydrolyzed. Then the steroids are extracted and converted to azodyes by reacting with the diazonium salt dark blue r. After separation by thin layer chromatography the azodyes are measured by remission analysis with a chromatogramm spectrophotometer. From the data obtained from 66 cases norm groups were set up for the excretion of the steroids in the 3rd trimester of pregnancy. In the last month of pregnancy the average excretion, expressed in % of excreted estriol, is as follows: estetrol 5,7%, 16-epiestriol 3,1%, 16-ketoestradiol 7,0%, 16-hydroxyestrone 5,3%.


[Specific determination of estriol-16-glucuronide from the urine of pregnant women in the last trimester].

A method for quantitative estimation of estriol-16-glucuronide in urine of pregnant women is given. The glucuronide is isolated by precipitation with ammoniumsulfate (70% w/v) followed by extraction with ether-ethanol (3:1). The estriol-16-glucuronide is converted with dark blue r to an azodye, which is separated from colored impurities by passing through a small column of sodium sulfate. The absorbance of the eluted dye is measured at 520 nm. 75 cases were analyzed and it was found that the estriol-16-glucuronide excretion increases in the 3rd trimester of pregnancy from the average value of 9.06 mg/24 hours in the 28th week to 22.11 mg/24 hours in the 42nd week of pregnancy.


Studies on extrahypophyseal sites of estrogen action in the induction of ovulation in rats.

To discover possible extrahypophyseal sites of estrogen action in the induction of ovulation, the influence of a s.c. injection of estradiol benzoate (EB) on cell nuclear sizes in the limbic-medial preoptic continuum of progesterone-pretreated cyclic rats was evaluated. The ovulatory dose of 5 mug EB caused a significant increase of nuclear volumes in the medial preoptic nucleus and the anterior and posterior parts of the medial amygdaloid nucleus. Precocious ovulation was induced in prepuberal female rats by unilateral implantation of a molten EB: cholesterol mixture into the posterior part of the mediocortical amygdala (PMCA), but not by implantation into the anterior part of this region (AMCA) or the medial preoptic area (MPA). In adult females injected s.c. with 2.0 mg progesterone on the day post estrus, bilateral implantation of 0.1 or 0.2 mug crystalline EB on the following day did not abolish the delaying effect of progesterone on the preovulatory LH increase and ovulation, when the implants were located in the MPA, lateral septum (LS), bed nucleus of the stria terminalis (BST), AMCA, PMCA or dorsal hippocampus (DHPC), whereas intrapituitary implants were highly effective. However, the bilateral introduction of large tallow pellets containing 0.1 mug EB each, into the LS, BST, AMCA or PMCA advanced ovulation in rats with progesterone-induced 5-day cycles. Equal pellets did neither induced ovulation nor an LH increase after implantation into the MPA or the DHPC. The results suggest that the anterior pituitary, mediocortical amygdala, BST and LS, but not the MPA or DHPC, are sites of the stimulatory feedback of estrogen on gonadotropin secretion in female rats, and that the amygdaloid response to estrogen differs between prepuberal and cyclic females.


Radioimmunoassay of plasma testosterone without chromatography.

A simple and rapid radioimmunoassay for determination of testosterone in peripheral plasma is described. A crude extract of the plasma is assayed directly without chromatography using an antiserum raised against testosterone-3-(carboxymethyl) oxime-bovine serum albumin. Accuracy and precision are satisfactory. Specificity is sufficient for the most purposes as has been demonstrated by comparison with a radioimmunoassay including chromatography.


The effect of ligation of cauda epididymidis and vasectomy on testicular function in the adult gerbil (Meriones hurrianae).

1. The effects of ligation of caput, cauda epididymides and vasectomy were studied in adult gerbils. 2. The operations were performed unilaterally, the testis and epididymides on the contralateral side serving as controls. 3. Ligation of cauda epididymides decrease testicular weight, whereas caput ligation did not change the testis weight. Accessory sex glands were reduced in size. 4. Ligation caused a drastic degeneration of the spermatogenic cells. There was a complete disruption of testicular function. Leydig cell hypertrophy was conspicuous. Caput and cauda ligation led to degenerative changes in the epididymides. Epididymal epithelium was regressed and the lumen was devoid of spermatozoa. 5. Caput and cauda ligation inhibited the synthesis of RNA, protein and sialic acid in testis and epididymides and depleted the fructose concentration in the seminal vesicle. 6. Vasectomy did not cause any alteration in sperm production during the 8 week period on the lighted side. The cytology and the biochemistry of the testis and epididymides appeared to be normal.


Pituitary cytology of radiothyroidectomised teleost Heteropneustes fossilis (Bloch.).

The pituitary of Heteropneustes fossilis is divisible into rostral (RPD) and proximal (PPD) pars distalis, and pars intermedia (PI). Neurohypophysis extensively ramifies in the PI. The RPD is formed of acidophilic prolactin cells and lead hematoxylin (H. Pb) positive ACTH cells. The latter is arranged around the neurohypophysial extensions. The PPD is comprised of thyrotrophs (TSH) and gonadotrophs which are stainable with PAS, AF, and aniline blue. Acidophilic somatotrophs (STH) and chromophobes are scattered throughout the PPD. In the pars intermedia PAS positive and H. Pb positive cells are present. The latter is believed to secrete MSH whereas the function of the former is yet to be confirmed. In the partly and completely thyroidectomised H. fossilis the TSH cells exhibited marked hypertrophy. They are located in the middle of the PPD flanked by the gonadotrophs on either side. Hypertrophy of the ACTH cells were also evident. But the other cell types did not show any marked changes as compared to the controls.


The porphyrin content of harderian glands in rats and the melatonin-melanocyte stimulating hormone-system.

Porphyrin contents of the Harderian glands were compared in groups of rats composed according to sex and age, exposed to continuous darkness or 3000 Lux illumination, or to changing natural illumination around the clock. All instances of melatonin-prevalence (e.g. absence of light, prepuberty) increased, those of melanocyte stimulating hormone decrease the porphyrin contents. Intraperitoneal injections of these hormones evoked analogous changes, followed by secondary inverse responses. Results are interpreted in terms of antagonism, equilibrium and circadian imbalance of the above hormones. Damping of the latter by the fluorescent light of the Harderian gland is suggested.


Alcohol inhibition of formalin induced depletion of neurosecretory material in the teleost Clarias batrachus (L).

In the normal C. batrachus a fair amount of stainable neurosecretory material (NSM) is always present in all the component parts of the hypothalamo-neurohypophysial (HN) complex. When formalin was injected intraperitoneally 70 to 90% of the NSM was depleted from the HN complex. When ethyl alcohol was administered immediately after formalin treatment, the depletion of NSM was inhibited, and their staining intensity could be compared with those of untreated controls.


[Deiodase activity in rats following an overdose of thyroid hormone].

The L-DIT and L-T4 deiodinating activity in supernatants from liver or kidney homogenates of normal rats or rats loaded with T4, T3 or TSH, was investigated. Deiodination of L-DIT occurs in liver supernatants twice as much as in liver, referring to mg of protein of g of tissue, while the deiodination of L-T4 seems rather equal. The over all rate of deiodination, however, reaches in liver for L-DIT the threefold, for L-T4 the fivefold value, as compared with kidney. Short periods of loading do not alter deiodination of L-DIT in liver or kidney at all; but lead to significant elevation of L-T4-deiodination in liver tissue. Higher doses or longer periods of loading cause a significant rise of L-DIT-deiodination in liver and kidney, while the L-T4-deiodination in liver is significantly decreased and in kidney significantly elevated.


Studies on 5'-nucleotidase activity in blood serum, tissues and liver mitochondrial fraction of normal, hypo- and hyperthyroid rats.

Clinical and experimental studies have previously shown the effect of thyroid state on the activity of non-specific phosphohydrolases. This research was undertaken to determine the influence of thyroid hormones on the activity of specific phosphohydrolase-5'-nucleotidase. The activity of 5'-nucleotidase was estimated in blood serum, tissues (liver, kidney, lung, brain) and mitochondrial fraction of liver of normal, methylothiouracil-induced hypothyroid and thyroxin-induced hyperthyroid rats of Wistar strain. The experiments have shown that the hypothyroid state induced decrease of the activity of 5'-nucleotidase in all studied materials, and on the contrary, the hyperthyroidism induced the increase of the enzyme activity. The hypothetical mechanism of the effect of thyroid hormones on the processes of feed back regulation of oxydative phosphorylation and delivery of substrates and oxygen is presented. The key role of 5'-nucleotidase in this mechanism is discussed.


Effect of different doses of ascorbic acid on thyroid activity in rats at different levels of dietary protein intake.

Rats, which can synthesize vitamin C, react similarly to graded doses of ascorbic acid as guinea pigs. Low doses of ascorbic acid stimulate and high doses inhibit the thyroid activity of rats which are supplied with normal and high percentages of protein. The stimulatory effect of low doses of ascorbic acid on hyperactive thyroid of high protein fed animals is additive. Ascorbic acid has no significant effect on the thyroid of low protein fed animals (deficient diet supplied for 21 days). In the initial stages of protein deficiency (deficient diet supplied for 11 days) the effectiveness of vitamin C on thyroid of rats was still significant. Deiodinase enzyme activity of peripheral tissues is markedly reduced in animals supplied with 2% of protein for 21 days, but this effect is less intense in animals supplied with 2% of protein for 11 days.