Effects of propranolol on haemodynamic changes and gas exchange at rest, in orthostasis, and on exercise in patients with arterial hypertension. The effects of propranolol on the circulation and respiration were studied in 38 patients with essential hypertension and symptomatic renal hypertension. The hypotensive effect of propranolol was associated with decrease in the cardiac index and heart rate; the peripheral vascular resistance moderately increased, and the circulating blood volume and haematocrit value showed no essential changes. Besides, a prolongation of the pre-ejection period, the decrease of intrasystolic index, an increase in the myocardial wall-tension index, and a retardation of the elevation rate of the intraventricular pressure were observed. After propranolol medication, on transition into the vertical position the heart rate showed a less marked acceleration; the remaining haemodynamic parameters changed in orthostasis as they had done before the treatment. After propranolol medication, on exercise the systolic and mean arterial pressures, heart rate, and cardiac output exhibited lesser increases than before the treatment, whereas the circulating blood volume, diasolic pressure, and peripheral vascular resistance increased just as they had done before the treatment. At rest, during propranolol medication there appeared a certain tendency to decreased oxygen uptake; in orthostasis the degree of increase in oxygen uptake did not change by the action of propranolol. Besides, propranolol did not alter the blood-plasma levels of lactic acid and pyruvate at rest and did not essentially change the oxygen uptake during exercise. The level of lactic acid and the lactate/pyruvate quotient in plasma during exercise increased slightly less after than without propranolol.


Myocardial blood flow in mitral valve disease and in primary congestive cardiomyopathy, and its relation to some haemodynamic indices. Myocardial blood flow was estimated using the technique of selective xenon-133 solution injection into the coronary artery, in 20 patients with mitral stenosis, 8 patients with mitral insufficiency, 8 patients with primary cardiomyopathy, and in 7 healthy subjects. The mean value of myocardial blood flow in mitral stenosis (60.9 +/- 10.5 ml/min/100 g) and in mitral insufficiency (58.5 +/- 7.7) did not differ from the mean value obtained in the control group (66.0 +/- 9.1). On the other hand, myocardial blood flow in primary congestive cardiomyopathy was significantly diminished (54.1 +/- 8.6). Myocardial blood flow was also lowered in patients with class IV of heart failure (48.3 +/- 7.6), as compared to healthy subjects. A positive correlation was found between myocardial blood flow and the left ventricular work index (r = 0.48, p less than 0.05), as well as between myocardial blood flow and the right ventricular work index (r = 0.47, p less than 0.05). A weak correlation was noticed between myocardial blood flow and left ventricular end-diastolic pressure (r = 0.38, p less than 0.05), as well as between myocardial blood flow and right ventricular end-diastolic pressure (r = 0.34, p less than 0.05).


Some properties of adenosine deaminase from vascular smooth muscle and its inhibition by various vasodilators. Because of some uncertainties still existing about the role of adenosine deaminase in the drug-influenced adenosine breakdown, the authors isolated this enzyme from vascular smooth muscle and studied the inhibition of its activity by some vasodilating drugs. The adenosine deaminase was purified 360-fold from bovine carotid artery by means of (NH4)2SO4-precipitation, heat treatment, and gel filtration. This enzyme behaves in a similar way as preparations of the same enzyme from other tissues in respect to pH-dependence and Michaelis constant. The vascular enzyme is inhibited by dipyridamole and trapymine in a competitive manner, hexobendine and lidoflazine are without any effect. The results lead to the conclusion that the inhibition of vascular adenosine deaminase does not constitute the sole cause of the adenosine-potentiating effect of the vasodilating drugs studied.


Coronary circulation in experimental traumatic shock, and effect of some vasoactive agents on its parameters. On 35 heparinized cats with experimental traumatic shock induced according to Cannon, changes in the coronary blood flow, produced by intravenous injections of noradrenaline, angiotensin, hydrocortisone, histamine, and serotonin, were studied. Traumatic shock was characterized by decreases in the coronary blood flow and organic oxygen uptake, despite a simultaneous decrease in the regional vascular resistance. Injections of noradrenaline (14-18 mug/kg) and angiotensin (29 mug/kg) induced, both in the initial normal state and in shock, increases in the coronary blood flow rate and in the regional oxygen uptake; an injection of hydrocortisone (7.1 mg/ml) produced similar effects in the normal state, but did not elevate the oxygen uptake in shock; an injection of histamine (32 mug/kg) had no effect on the coronary blood flow rate, but reduced the regional oxygen uptake both in the normal state and in shock; an injection of serotonin (30 mug/kg) exerted no major effects on the blood flow. The results obtained might serve as guidelines for pharmacological regulation of coronary circulation in shock.


Distribution of the femoral circulation in living dogs. The femoral circulation of living dogs was studied with plastic carbonized microspheres 50 and 200 micra in diameter, labeled with Yterbium169. The femoral blood flow is distributed in the following way: 35% of the particles 50 micra in diameter went to muscle, 45% of the same particles went to skin and 20% to bone. When the particles were 200 micra in diameter 16% went to muscle, 65% to skin and 19% to bone.


Speech and memory assessment in psychomotor epileptics. Thirty post-lobectomy patients operated on for relief of seizures due to temporal lobe epilepsy and six patients who had had implantation of depth electrodes only were assessed in terms of their speech and memory abilities. The results from two subtests of the Boston Diagnostic Aphasia Examination show no significant group differences on speech tests. On the other hand, patients with left or dominant temporal lobectomies showed a greater memory deficit than those operated upon on the right or non-dominant side. This difference was apparent on tests of both recent verbal memory and long-term memory.


Recognition memory in amnesic patients: effect of temporal context and familiarity of material. In Experiment I recognition memory for pictures, high frequency words and low frequency words was examined in Korsakoff patients and alcoholic controls at retention intervals of 10 minutes, one week and seven weeks. Korsakoffs showed (1) surprisingly good recognition of pictures and low frequency words, scoring well above chance even at the longest retention interval; (2) no evidence of a faster than normal rate of forgetting. In experiment II the familiarity of pictures was varied in such a way that correct recognition involved either (a) explicit decisions as to whether items were seen 10 minutes or 24 hours previously or (b)decisions as to whether items had ever been seen before. Korsakoffs were severely impaired in making the first type of discrimination but had little difficulty with the second type. It is suggested that the primary defect in amnesia may concern contextual memory rather than memory for items as such.


Interset variability on the raven coloured progressive matrices as an indicator of specific ability deficit in brain-lesioned patients. Patients with right cerebral lesions were found to have lower RCPM scores than a matched group of patients with left lesions. Analysis of interset patterns of performance demonstrated relatively greater difficulty for right lesion patients, especially those with posterior lesions on the Ab set. The findings were interpreted in terms of the abilities that Raven maintains underly test performance.


Visual field recognition memory for right-handed females as a function of familial handedness. Recognition memory for nonsense words presented vertically and unilaterally in the left and right visual fields was investigated in right-handed females as a function of the memory interval and familial handedness. The subject decided whether another nonsense word presented in central vision after memory intervals of 0, 5, or 10 sec. was the same as the stimulus word. The exposure duration producing a recognition accuracy of about 75% for each subject was employed and ranged from 5 to 28 msec. Right-handed females with only right-handed family members demonstrated right visual field superiorities indicative of a slight left hemisphere specialization for memory but not for reception of verbal material. Field superiorities obtained for right-handed females with a left-handed parent or sibling were not significant. In general, less complete lateralization of linguistic function in females was indicated and the importance of familial handedness in cerebral asymmetry of function was confirmed.


Some relations of grammar and lexicon in aphasia. A new form of a Sentence Order Test was applied to a group of Broca's, Wernicke's and total aphasics. Sentences cut into three movable cards should be put together. Some of the sentences could be arranged in two different ways. Broca's aphasics prefered to order the parts according to a logical string of lexical items neglecting the grammatical errors. Wernicke's aphasics arranged the material according to the grammatical structure being unaware of the odd lexical meaning. Most of the results of total aphasics were similar to those of Wernicke's aphasics others however performed like Broca's aphasics.


Paired associate learning of Morse code and Braille letter names by dyslexic and normal children. Twenty dyslexic and twenty normal children, matched for age and sex and with the same mean I.Q. were tested on their ability to learn letter names of Braille configurations presented visually or tactually and to Morse Code signals presented aurally. The dyslexic Ss learned fewer letters in all three modalities although for both groups the visual-verbal method was easiest. The deficits were not attributable to specific modality dysfunction nor to a failure of intersensory integration. More general encoding and retrieval difficulties appear to be implicated.


Hemispheric specialization for speech perception in four-year-old children from low and middle socio-economic classes. Four-year-old male and female children from low and middle socio-economic class (SEC) were presented a dichotic syllable task. Both low and middle SEC males evidenced significant right-ear advantages. Neither low nor middle SEC females evidenced a significant right-ear advantage. The similar ear advantage in the low and middle SEC populations replicates a previous study with six-year-olds and suggests that the variations in rearing conditions which occur in low and middle SEC classes does not affect hemispheric lateralization for speech perception.


Toxicological studies on azapropazone.

Toxicological studies on azapropazone. The toxicity of azapropazone, a non-steroidal anti-inflammatory analgesic compound was studied in mice, rats, hamsters, guinea pigs, rabbits, cats, mongrel and beagle dogs, domestic pigs, rhesus monkeys, cynomolgus monkeys and baboons in experiments which ranged from acute, single-dose studies up to treatment periods of 1 year. The beagle dog was found to be especially sensitive to gastro-intestinal ulceration from azapropazone and this contrasted with the marked lack of gastro-intestinal hazard to other animals and particularly to the 3 primate species studied. The animal experiments did not indicate any potential risk to other body systems, and comparisons  with other anti-inflammatory compounds, where these were made, suggest that azapropazone is at least as safe as other commonly-used agents. Azapropazone was not found to have teratogenic, carcinogenic or antimitotic activity and was shown not to produce local tissue damage.


The determination of azapropazone in blood plasma. Three methods for the determination of azapropazone were studied for the analysis of blood plasma samples taken after oral administration of azapropazone. A gas chromatographic method was compared with two simple spectrophotometric assay methods and the effect of metabolites of the drug on each method is described. It is concluded that metabolites are unlikely to cause significant interference with the two simple methods and that either is suitable for determination of plasma levels of the drug. Some problems associated with a gas chromatographic method are described and the comparative results of the examination of plasma samples using these methods are given.


Long-term use of azapropazone in rheumatoid conditions. In an open assessment of azapropazone, 51 patients with rheumatoid disorders, mainly rheumatoid arthritis, were treated continuously for periods up to 3 years (range 2 weeks to 38 months). Treatment was interrupted or discontinued in 9 patients for various reasons. Initial dosage was 1200 mg. daily, but this was usually reduced after a few months to a maintenance level of 900 mg. daily. An overall assessment of patient response at the end of the study period indicated that only 4 (7.8%) of the 51 patients failed to obtain satisfactory relief during treatment: 28 (54.6%) showed objective signs of improvement, such as reduced joint swelling and stiffness, as well as subjective evidence of symptom relief, and a further 19 patients (37.3%) reported an equivocal analgesic effect with azapropazone. Few side-effects were reported, mainly mild gastralgia and nausea, and routine laboratory investigations throughout the long-term study revealed no abnormalities in the blood picture, liver or renal function or coagulation factors. There was also no evidence of any interaction between azapropazone and other drugs used concomitantly.


Life style and nutrient intake in the elderly. The life styles of the elderly population under study indicate that they had positive attitudes toward health in general and toward food and eating, Their food habits and beliefs were free from faddism, they were willing to try new foods and to change at least some of their food habits, and they had a good appetite for meals. Meal patterns and choice of foods, snacks, and food likes were toward foods of high nutritive value. They had comparatively few food dislikes, and the majority ate three meals a day. Many of the participants in this study had nutrient intakes of less than two-thirds the 1974 RDA'S. Food choices, meal patterns, and beliefs about food suggest that economic factors strongly influenced dietary adequacy and limited the food choices and size of servings. Black females appear to be the most disadvantaged group. All of these findings are a strong indicator of the need for group feeding programs for the elderly. Such meal programs should provide at least one-third of the daily nutrient needs, and should be pleasurable experiences using foods appropriate to the food habits and beliefs of the specific groups, their locale, and their cultural-economic backgrounds. These programs should also be accompanied by realistic nutrition education programs designed to provide guidance in buying and using foods of highest nutritive value within their resources. The need for such programs becomes increasingly urgent because of today's rapidly increasing food prices.


Avoiding malpractice suits through the use of informed consent. The doctrine of informed consent is based on a long tradition of promoting self-autonomy and rational decision-making. The amount of information required to be disclosed by the doctor to the patient is that which permits the patient to decide for himself whether or not to undergo the recommended treatment. It includes information about risks of death or serious bodily harm, probability of success, problems of recuperation, and alternative modes of treatment. Disclosing such information contributes to the doctor-patient relationship and therefore makes recourse to malpractice litigation in the face of an unsatisfactory or untoward result less likely. Attempts to abolish the doctrine are potentially counterproductive and could lead to widespread mistrust of the medical profession on the part of a society that increasingly demands more information in all areas. Physicians will best serve both themselves and their patients by fully disclosing all relevant information before asking patients to consent to specific therapies.


Clinical comparison of two electronic spirometers with a water-sealed spirometer. Two electronic spirometers which use a hot-wire anemometer to measure air flow were clinically compared with a water-sealed spirometer. The forced vital capacity (FVC), the forced expiratory volume in one second (FEV1), the FEV1/FVC%, the mean forced expiratory flow between 200 and 1,200 ml of the FVC, the mean forced expiratory flow during the middle half of the FVC, the mean forced expiratory flow between 75 and 85 percent of the FVC, and the maximum voluntary ventilation were determined for a group of 67 subjects. Techniques are described for connecting the spirometers in series  to permit evaluation by human subjects or by syringe injection. High correlation coefficients generally were obtained when comparing the electronic spirometers with the water-sealed spirometer, but the actual range of percent difference was greater than 11 percent in all spirometric tests. The results indicate the need for systematic evaluation of electronic spirometers to characterize their deviation from accented standards. Frequent calibration is necessary to maintain consistent performance.


Painless ST-segment depression in patients with angina pectoris. Correlation with daily activities and cigarette smoking. Ambulatory electrocardiographic monitoring was employed in 33 patients with angina pectoris and abnormal stress tests to determine the frequency with which myocardial ischemia manifested by painless ST-segment depression occurred during normal activity. ST-segment depression occurred in 24 patients during the monitoring period; and in 21, it occurred either solely in the absence of pain or both with and without pain. Of 109 recorded episodes of ST-segment depression, 61 percent were painless. The frequency of painless ST-segment depression was independent of activity other than automobile driving, during which all episodes were painless. In patients who smoked cigarettes, ST-segment depression was more common while smoking, but the incidence of painless ST-segment depression was not altered. The study indicates that ST-segment depression occurs more commonly in the absence than in the presence of chest pain and that ambulatory electrocardiographic monitoring is a useful method of determining the frequency of myocardial ischemia during normal daily activity.


Development of "resistance" in beta-adrenergic receptors of asthmatic patients. Complete in vitro dose-response curves for  (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No "resistance" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors.


Effect of exercise on left ventricular ejection time in patients with prolapsing mitral leaflet syndrome. The effect of exercise on left ventricular ejection time was determined in 12 subjects with prolapsing mitral valve leaflet syndrome (PML). A single lead ECG (CM5), phonocardiogram and carotid pulse contour were recorded simultaneously with the subjects at supine rest before and immediately after multistage treadmill exercise. Systolic time intervals were measured from five consecutive complexes to determine the pre-ejection period (PEP), left ventricular ejection time (LVET) and total electromechanical systole (QS2). LVET was corrected for heart rate and defines as LVETc. In nine subjects, an increase of 1 to 49 msec was observed in the LVETc following exercise. A shorter resting LVETc and greater afterload at peak exercise was related to an increase in LVETc of 10 msec or more. Exercise elicited or evoked evidence of left ventricular dysfunction. The results support the concept that impaired left ventricular performance is a concomitant of this syndrome.


Pacemaker-induced change in prosthetic valvular sounds. Variable intensity and timing of valvular sounds were noted in two patients with permanent pacemakers and prosthetic valves. In the first patient, who had a mitral and a tricuspid prosthesis, valvular opening sounds became widely separated with a change from nodal to ventricular paced rhythm. In a second patient, who had a mitral prosthesis in sinus rhythm with first-degree atrioventricular block, a very quiet closing sound increased markedly in intensity with the onset of ventricular pacing. The mechanism for these changes is described using a technique which at brief intervals throughout the cardiac cycle permitted documentation of simultaneously recorded phonocardiogram, electrocardiogram, and pulse tracings with a visible image of the prosthesis. In the usual patient with a prosthetic valve auscultatory changes should arouse a suspicion of malfunction; however, in the relatively uncommon patient with a prosthesis and an artificial pacemaker, it should be recognized that auscultatory changes may well have a physiologic explanation.


Focal myocytolysis mimicking the electrocardiographic pattern of transmural anteroseptal myocardial infarction. Two patients are documented, one with a cerebral infarct and one with a primary brain tumor, both of whom initially had a normal electrocardiogram but subsequently developed the classic pattern of transmural anteroseptal myocardial infarction; however, in both cases the autopsy proved the electrocardiograph pattern to be related to "focal myocytolysis" of the myocardium. Both patients also exhibited coronary arterial disease of the localized type and to a maximal luminal narrowing of 75 percent without a history of anginal complaints. It is of interest that the intensity of the lesions of focal myocytolysis was greatest in the areas supplied by the affected arteries. This peculiarity suggests that ischemia, though not primarily involved in inducing the lesions, could be of additional significance.


Pulmonary fibrosis associated with tracheobronchial aspiration. A study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology. Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fibrosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux. The incidence of both hiatal hernia and reflux were statistically higher in the study group than in a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications; (2) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases; and (3) a subgroup of 23 patients with pulmonary fibrosis of established etiology. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum-mid-expiratory flow rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobronchial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis.


Xerotomography of peripheral lung lesions. Xerotomography was compared to conventional tomography in 72 patients with peripheral lung lesions. The xerotomogram was superior to the conventional tomogram in 41 patients, and yielded no additional information in 31. Details of lesions were better displayed, especially the margins: cavitations, air bronchogram and bronchiectasis, and calcification. Differentiation between benign, inflammatory and malignant lesions was facilitated. The xerotomographic process improved the image detail of lesions due to the edge enhancement property and the greater recording latitude of contrast of the xeroradiographs. Xerotomography is recommended only in selected patients for a few tomographic cuts because of the high radiation dosage.


Left axis deviation: diagnostic contribution of stress testing and post-exercise systolic time intervals. The response to graded submaximal upright bicycle ergometry combined with resting and postexercise systolic time intervals (STIs) was investigated in ten ambulatory subjects (study group) with normal electrocardiograms except for a frontal plane axis of greater than or equal to -30 degrees, or left axis deviation (LAD) mean -40 degrees); and eight age-matched volunteers (control group) with a normal ECG and frontal plane axis (mean +35 degrees). Following a 12-lead resting ECG, supine STIs were measured. The subjects then exercised on a bicycle ergometer at progressive workloads with ECG and blood pressure monitoring until a heart rate based on 85 percent of tha age-predicted maximum was attained or an abnormal end point was noted. STIs were repeated immediately postexercise. Prolongation of left ventricular ejection time corrected for heart rate (LVETc) of 8 msecs or more from rest to post-exercise. (deltaLVETc) was considered an abnormal STI response. The deltaLVETc can elicit left ventricular dysfunction and possible latent organic heart disease in patients with isolated left axis deviation.


The role of hypovolemic stress in the production of fat embolism in rabbits. 1. Morphologic alterations of the lungs. In rabbits, an experimental model of fat embolism was produced that simulates the course of events in the clinical situation. Small doses of fat-cell suspension (0.075 ml/kg of body weight), prepared by collagenase treatment of homologous adipose tissue, were injected intravenously. Concomitantly, hypovolemia was produced in two animal groups by either withdrawing 20 percent of the estimated blood volume or by application of a hind-limb ischemic tourniquet for 90 minutes. The presence of pathoanatomic characteristics typical of fat embolism was evaluated by recording lung/body weights, macroscopic appearance, and semiquantitative microscopic estimation in the lungs of edema, hemorrhage, atelectasis, intravascular coagulation, and leukocytic thrombi. Mean indices of lung/body weight were higher in all animals receiving injections of fat-cell suspension, as compared to controls. The score for microscopic generalized pulmonary damage was significantly higher in rabbits exposed to both fat-cell injections and hypovolemia than in controls or after fat-cell injections alone. It is concluded that hypovolemia enhances the development of fat embolism in rabbits subjected to small doses of fat-cell suspension.


Lung abscess and osteomyelitis of rib due to Yersinia enterocolitica. The first reported case of infection of the lung and bone with Yersinia enterocolitica is described. This organism has only recently been known to infect humans. Although a wide spectrum of diseases has been described, all have appeared to be relatively benign; however, in our case a rapid necrotizing process occurred. Therefore, the aggressive nature of this organism outside its usual surroundings, eg, the gastrointestinal tract, is worth noting.


Ectopic origin of the left anterior descending coronary artery from the right coronary sinus. Report of a case simulating anterior descending obstruction. A patient with anomalous aortic origin of the left anterior descending coronary artery was studied. The clinical picture and the preliminary angiographic findings simulated obstruction of the left anterior descending coronary artery near its origin. Careful catheter exploration of the right coronary sinus led to the correct diagnosis, emphasizing the importance of complete visualization of all branches of the coronary tree, including distal radicles of a supposedly occluded vessel.


Congenital levojuxtaposition of the right atrial appendage. Association with persistent truncus arteriosus, type 4. Congenital levojuxtaposition of the right atrial appendage is a rare malformation most commonly associated with a transposition of the great arteries. We report a case of levojuxtaposition of the right atrial appendage associated with a persistant truncus arteriosus, type 4. Juxtaposition of the atrial appendage is a sign of severe cyanotic congenital heart disease, and this is best diagnosed by a selective right atriogram or superior venacavogram.


Bronchiectasis following heroin-induced pulmonary edema. Rapid clearing of pulmonary infiltrates. We observed a patient who developed diffuse bronchiectasis subsequent to heroin-induced pulmonary edema. Unlike the previously reported cases, there was rapid clearing of pulmonary infiltrates and little evidence of severe aspiration. The development of bronchiectasis was attributed to a bronchial infection subsequent to clearing of the pulmonary edema. Physiologic dysfunction was characterized by marked obstruction, pulmonary hypertension, and mild hypoxemia.


Monocular blindness secondary to calcific embolization. An unusual presentation of rheumatic mitral valvular disease. This report of a patient with systemic calcific embolization resulting in nonocular blindness represents an unusual presentation and complication of mitral valvular disease.


Viral inclusion bodies in tracheobronchial epithelium of asymptomatic subjects. During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.


Sick sinus syndrome requiring permanent pacemaker implantation in a patient with mirror-image dextrocardia. A patient with the sick sinus syndrome accompanying mirror-image dextrocardia which was associated with double superior venae cavae and an absent inferior vena cava is presented. A permanent transvenous demand pacemaker was inserted because of repeated episodes of dizziness and a documented 31/2-second period of asystole. Precise knowledge of the venous system and the location of the apex of the right ventricle was necessary prior to permanent pacemaker implantation.


Aspergilloma within a malignant pulmonary cavity. The simultaneous appearance of both bronchogenic carcinoma and aspergilloma with the typical radiographic appearance of a mycetoma emphasizes the importance of consistent suspicion for malignancy in any pulmonary lesion. This is apparently the first reported case in which allergic phenomena (asthma-like symptoms and eosinophilia) are associated with an aspergilloma occurring within a cavitary bronchogenic carcinoma.


Application of systolic time intervals to acute cardiomyopathy with echovirous 2. The occurrence of echovirus type 2 myocarditis in an adult is reported. Myocarditis was substantiated by abnormal electrocardiograms. More important, a prolonged course and severe functional impairment was quantitatively assessed by serial systolic time intervals, even after the ECGs became normal. The patient also had meningitis, hemiparesis, and convulsions. Viral isolation was from the spinal fluid.


Anomalous communication of the left coronary artery with a peripheral branch of the right pulmonary artery. A 64-year old man had a history of two myocardial infarctions recurrent episodes of paroxysmal ventricular tachycardia and hemoptysis. Cineangiocardiographic studies showed an anomalous vessel connecting the left coronary artery with a peripheral branch of the right pulmonary artery. Although several coronary obstructive lesions and abnormalities in the distribution of the circumflex branches were found, the anomaly apparently produced a real "pulmonary steal" and, thereby a worsening of the coronary insufficiency. We believe that this is the first reported case in the literature with such a coronary-pulmonary fistula. The angiographic findings are presented in detail, and the possible factors in the development of myocardial ischemia are discussed.


Is the centromeric heterochromatin of Mus musculus late replicating? Quantitative analysis of DNA replication in embryonic cultures of C57BL/6J mice was carried out, using autoradiography after tritiated thymidine incorporation. The centromeric regions are late-replicating.


Qualitative and quantitative EEG in psychotic children. The EEGs of hospitalized psychotic boys were analyzed quantitatively by means of visual evaluation, analog frequency analysis, and digital computer period analysis and were compared with those of age- and sex-matched normals. Visual evaluation of the records demonstrated that psychotic children have significantly more beta activity as well as fewer alpha bursts than  normal controls. EEG analog frequency analysis showed that psychotic children have a greater percentage of total voltage in the 3-5 cps and 13-33 cps bands, while they show less voltage in the 6-12 cps bands as compared with normal controls. Digital computer period analysis demonstrated more slow, less alpha, and more fast activity, as well as a greater average frequency and frequency deviation in both the primary wave and first derivative measurements in psychotic children than normals, while normals showed a trend towards higher amplitude and amplitude variability. The similarity of the EEG differences between psychotic and normal children to those differences observed between adult chronic schizophrenics and normals, as well as to those between children of "high risk" for becoming schizophrenic and controls, suggests that the above described findings are characteristic for the pathophysiology of schizophrenia.


Epidemiology of tardive dyskinesia. Part II. In the part II of an epidemiological study on tardive dyskinesia performed on the same sample of 332  chronic schizophrenic patients (142 males and 190 females), the authors come to the conclusion that the prevalence of tardive dyskinesia is significantly higher if the mean age was higher at the beginning of treatment with sedative or incisive neuroleptics, their combinations (cocktails) and added antiparkinsonian drugs. Age seems to be the most important factor in the prevalence of tardive dyskinesia. The mean longer duration of "incisive" free intervals significantly decreases the prevalence of tardive dyskinesia. Other factors analysed in our sample, especially the total amount of neuroleptics administered, the type of neuroleptics and the mean duration of neuroleptic treatment, do not play a significant role in the prevalence of tardive dyskinesia.


Alcoholism, alcohol, intoxication and assaultive behavior. The use of alcohol and the role of alcohol intoxication in the crime was studied in 307 males entering the North Carolina prison system after conviction of serious assaultive crimes. The majority (80%) were convicted of homicide (1st and 2nd degree murder and manslaughter), and the remainder (20%) committed a variety of felony assaults. Only 8% of the subjects were abstainers, and 36% were problem drinkers. The problem drinkers often had previous arrests for alcohol offenses (70%) and also were more likely to have previous nonalcohol criminal records (67%) and previous serious assaults (50%) than were other subjects. The problem drinkers were unlikely to have been engaged in treatment of alcoholism (13%) and almost never voluntarily sought treatment. The majority (58%) of the subjects were definitely drinking at the time of the crime, and a substantial number (40%) of the victims were definitely drinking at the time of the assault. Amnesia for the cime was uncommon (13%) among those who were drinking; but of those subjects who did claim amnesia, almost all had been drinking. Alcohol use appeared to be a significant ingredient in the production of the assaultive behavior in the majority of the cases. The majority of the subjects who were intoxicated at the time of the crime did not consider their state of intoxication as relevant to their behavior in spite of the seeming advantage to do so.


Psychiatric consultations in a general hospital. A report on 1,000 referrals. 1,000 medical and surgical inpatients referred for psychiatric conSULTATION SHOWED CONCURRENT PHYSICAL AND PSYCHIATRIC DISORDER IN 68.2% of cases. This is in accordance with epidemiological findings that these two types of morbidity have a positive association and coexist in 20-50% of patients. Depression was the commonest psychiatric disorder in all classes of organic disease and accounted for 53% of all psychiatric diagnoses. Organic brain syndromes, acute and chronic constituted 18% of referrals. Almost twice as many women as men were referred despite their nearly equal distribution in hospital population. One-third of the females had no positive medical diagnosis compared to one-fifth of the men. Alcoholism was a major problem in 8.9% of referrals. 7.8% of patients were referred following suicidal attempt. Of the 50 patients with cancer. 66% had depression. Too few medical patients with psychiatric complications are referred and adequately treated. Greater emphasis on teaching psychiatric syndromes is called for. Psychiatric consultation-liaison services offer the most direct form of collaboration between psychiatry and medicine in the interests of comprehensive patient care.


Psychiatric disorders and crime: a study of pretrial psychiatric examinations. A study of 50 consecutive individuals referred for pretrial psychiatric examination, presumably because of previous psychiatric hospitalization (82 percent), indicated that antisocial personality, alcoholism, or drug dependence was present in 80 percent. Schizophrenia or bipolar affective disorder was seen in about a third of the subjects, usually associated as well, however, with antisocial personality, alcoholism, or drug dependence. There were no significant differences in index crime between those with or without schizophenia bipolar affective disorder. It is concluded that the latter conditions occur in no more than two or three per cent of all felons.


[Treatment, follow-up and prognosis of drug addiction (author's transl)]. Using a standardised psychological questionnaire (self-estimation scale, personality-inventory FPI of Fahrenberg and Selg) and serial examinations, the effectiveness of a therapeutic concept combining drug, environmental and group therapy was tested. The psychological parameters objectified stabilisation of the psychological-autonomic and emotional areas as well as ego functions. The follow-up study extended over an average of five years and included 101 former drug addicts (14 could not be interviewed, 10 had died). Social stability was observed in 63% (satisfactory working performance, reduction of sexual problems, contacts with friends). 36% of the group had abstained from further drug taking, 27% were taking them periodically, 32% had to be treated again and 5% had deteriorated (trend towards invalidism).


[Results of pacing after acute myocardial infarction (author's transl)]. Indications for electrical pacing were present in 58 of 665 patients with acute myocardial infarction (8.7%). Posterior-wall infarction had occurred in 34, anterior-wall infarction in 20, while two had combined infarction and in a further two precise localisation was not possible. There were 16 deaths (27.6%), six of them with posterior-wall and nine with anterior-wall infarction. Bradycardic arrhythmias with A-V block predominated among posterior-wall infarctions, hemiblocks and bifascicular block in anterior-wall infarctions. Permanent pacing was practised in 14 patients, 11 with posterior and three with anterior-wall infarctions, i.e. permanent pacing was four times as common after posterior than anterior-wall infarctions, the proportion being 2:1 for temporary pacing, largely due to a higher mortality-rate after anterior-wall infarction. Old anterior-wall scars were present in nine of eleven patients with permanent pacing. Because of the danger of late bradycardia or A-V block patients with posterior-wall infarction should be carefully followed in the late phase (from about the third week onwards), especially if it is known that they have an old anterior-wall infarct.


[Cytogenetic and clinical findings in suspected Turner's syndrome: results of a five-year study of 207 patients (author's transl)]. The hallmark of Turner's syndrome is small stature, primary amenorrhoea with delayed puberty and other congenital defects. Cytogenetic examinations were done over a five-year period of 207 patients of different ages. The diagnosis of Turner's syndrome was confirmed by karyotype in 94 (45.4%), tentatively confirmed by X-chromatin in 11 (5.3%) and in 21 (10.1%) with other disorders involving disturbed sexual development. In 73 cases Turner's syndrome was excluded and in nine the investigation had not been completed by the end of the study. There was a wide spectrum of clinical and cytogenetic findings in the 94 patients with cytogenetically confirmed Turner's syndrome: 50 (53.2%) had karyotype 45,X0; 25 (26.6%) X0/XX mosaic; 19 (20.2%) X-chromosomal structural anomalies with or without additional X0 cell line.


[Causes of electrode dislocation with transvenous pacemaker implantation (author's transl)]. The relationship between electrode dislocation and operative circumstances and case details was investigated in 486 patients who had pacemakers implanted. Electrode dislocation was more common among women and unrelated to age. The greater the operator's experience the lower the dislocation rate. Best results were obtained when implantation was performed via the left cephalic vein. There was a close relationship between threshold measurement obtained at the time of electrode placement and the frequency of dislocation.


[Cystinosis, hyperparathyroidism and metastatic calcifications (author's transl)]. An 11-year-old boy died from uraemia in the course of cystinosis. In addition to the renal lesions common to this disease he had also developed nodular hyperplasia of the parathyroids and widespread extra-osseous calcifications in lungs, kidneys, stomach, the muscular arteries, skin and subcutaneous tissue. The calcifications and other features suggest that the hyperparathyroidism was a "tertiary" one, although this term is not generally accepted. The unusual cutaneous calcifications were probably due to calciphylaxis. As in this case, hyperparathyroidism and calcinosis can develop into a "second disease" which, due to the cystinosis, may follow a remarkably autonomous course.


[Occupational allergy due to inhalation of pollen from Euphorbia fulgens Karw (author's transl)]. The increased cultivation and sales of Euphorbia fulgens Karw., originating in Mexico, has in the last few years led to occupational allergy, type I, in three growers manifesting itself as nasal disease, tracheobronchitis or bronchial asthma. Intracutaneous tests with pollen extracts were positive in all cases, even at high dilution. A specific hyposensitisation regimen, conducted over five months, gave highly promising results in one patient who had no symptoms in the following season, despite similar exposure. Such sensitisation by pollens of Euphorbia fulgens Karw. is probably widespread among growers and florists. The allergen is found only in the pollen, not in other parts of the plant. There is no relation to the toxic substances in the milk-sap of this plant family (Euphorbiaceae).


[Morphological and clinical results after combined hormone and radiation therapy for carcinoma of the prostate (author's transl)]. 83 prostatic carcinomas were analysed morphologically and clinically before and after combined therapy. The classification of these tumors is based on the proliferation pattern resulting in a group with only one and a group with a variety of growth patterns. The largest groups were carcinomas with glandular structures. On the basis of multiple biopsies the histologic regression of the tumors was determined. In 71% of the cases there was good agreement of morphological results and local palpation findings. Further analyses revealed a correlation between histological growth pattern of the carcinomas and degree of regression: prostatic carcinomas with glandular pattern showed more often a good regression after combined therapy than solid and(or) cribriform tumors. In the groups with a variety of structural pattern the degree of regression was dependent on the prevailing tumor structure. According to these results the organoid-glandular carcinomas of prostate are prognostically more favourable than all the other proliferation patterns. Nevertheless in a single case a prognosis of the therapeutic effect based only on the tumor differentiation can not be made.


[Serial studies of the long-term effects of a total-fasting regimen (author's transl)]. The long-term results of total fasting during hospitalisation were evaluated an average of 21 months after the end of the hospital stay in 42 patients treated for obesity between 1971 and 1975. Further weight reduction occurred in 14, while the remainder had regained some weight. Nine of the latter had, in fact, surpassed their prehospitalisation weight. Neither age not sex, social status, time interval since fasting had any influence on the long-term results of total fasting. It is concluded that, in view of the poor correlation between cost and long-term result of such total-fasting regimen, it should be undertaken in this form only exceptionally.


[Operative treatment of ulcerative colitis, Crohn's disease and diverticulitis (author's transl)]. Operations and follow-up examinations were conducted on 106 patient with ulcerative colitis, 33 with colitis Crohn, and 163 with diverticulitis, at the University Clinics of Cologne and Munich. Overall mortality rates were 24.5% (n=26), 6.1% (n=2) and 16% (n=26), respectively. In the surgical treatment of ulcerative colitis the possibility of malignant degeneration and,  in the case of Crohn's disease, prevention of recurrences must be taken into consideration. Whether Crohn's disease is a precancerous condition remains to be clarified. Choosing the optimal time for operative intervention is as important in diverticulitis as in ulcerative colitis. Because of the possibility of complications and the high risk of operation, early intervention is recommended for diverticulitis.


[Malpositioning of venous catheters (author's transl)]. The position of 2467 intravenous catheters was controlled radiographically over a period of one year. In 22.5% the position needed correcting. In most cases it was sufficient to withdraw the catheter slightly. In 68 patients in whom the catheter had formed loops or had entered the jugular vein the position was corrected using a J-shaped guide wire and was successful in 63 cases. This method needs little time and equipment and saves the patients repeated venous punctures. Not including bacterial contamination of the catheter the complication rate of venous catheterisation was 2.6%.


[Atrial flutter with an audible atrial sound (author's transl)]. In a case of rheumatic valve disease atrial sounds could be heard and recorded on the phonocardiogram during atrial flutter at a rate of 260/min and an atrioventricular block of 3:1 and 5:1. The atrial flutter sounds were also recorded in the apex-cardiogram and as a slight but rapid motion of the anterior mitral valve leaflet in the echocardiogram. These atrial sounds were recorded both in systole and diastole and disappeared after cardiac failure had been treated and sinus rhythm restored. This case and 19 others reported in the medical literature indicate that for atrial sounds to become audible requires high-grade atrioventricular block and increased atrial contractions with increased ventricular filling. The sounds have been proven to originate in the atrium, the characteristics of the sound being similar to those of an opening snap.


[Clinical features and course of congestive cardiomyopathy of unknown aetiology (author's transl)]. Clinical, haemodynamic and angiographic findings in 50 patients with congestive cardiomyopathy were related to subsequent clinical course (mean observation period of 40 months). Ejection fraction and changes in mean pulmonary "wedge" pressure on ergometric exercise proved to be the most reliable criteria for judging left-ventricular function. During the period of observation 11 patients had died, in 15 the clinical state had deteriorated by one or two functional classes, and in 24 there had been no change. Patients with progressing disease differed from those clinically unchanged by having a smaller cardiac index, increased end-diastolic left ventricular pressure, higher pulmonary arterial pressure and smaller ejection fraction. Prognosis was no worse with atrial fibrillation than with sinus rhythm. Four of 13 patients with left bundle branch block died during the observation period and in seven the clinical state had deteriorated by one or two functional classes. The tested variables apparently have a good prognostic value.


[Myocardial bridge - cause of cardiac phase-dependent coronary stenosis (author's transl)]. A 41 year-old man presented with anginal pain and a positive exercise electrocardiogram. Hemodynamic and angiographic evaluation disclosed mild hypertrophic obstructive cardiomyopathy and a conic stenosis of the proximal left anterior descending artery confined to the systolic phase of the heart action. The degree of constriction of the coronary artery was no longer evident. Pathophysiologic consequences suggest that surgical dissection of muscle bridges should be considered in symptomatic patients with severe coronary obstruction.


[Changes of left ventricular transverse diameter and of contractility after haemodialysis (author's transl)]. In 26 patients (8 women, 18 men; mean age 47 +/- 3 years) who participated in a regular dialysis programme twice weekly the left ventricular diameter, the mean velocity of fibre shortening, the ventricular wall thickness, and the muscle mass were determined echocardiographically. Left ventricular muscle mass (187 +/- 13 g), left ventricular posterobasal wall thickness (14,7 +/- 0,6 mm) and septal thickness (16,4 +/- 0,8 mm) were pathologically increased due to chronic pressure and volume overloading. After an average dialysis time of 12 hours the body weight was reduced by 2,6 +/- 0,4 kg (+ 1,0 to -7,8 kg). The left ventricular transverse diameter changed from 55,3 to 50,2 mm (P less than 0,001) which correlated with a decrease of the enddiastolic volume from 160 +/- 11 to 125 +/- 10 ml (P less than 0,01(. Despite increased cardiac frequency and unchanged diastolic and systolic pressure no significant increase of the mean velocity of fibre shortening (0,93 +/- 0,06 vector 1,13 +/- 0,09 circ/s) occurred. The results show that loss of fluid during haemodialysis led to a significant decrease of the enddiastolic transverse diameter and the enddiastolic left ventricular volume. However, dialysis does not lead to an increase of the mean velocity of fibre shortening as a parameter of improved contractility.


[Radiotelemetry of cardiovascular response on a fitness trail (author's transl)]. Continuous radiotelemetry of direct arterial blood pressure and heart rate was performed in eight healthy subjects (seven men, one woman; average age 26 years) on a fitness trail. The results demonstrate that such running represents a maximal effort, at 192/min heart rate (age-related maximum). The heart rate remained constant whether on largely dynamic exercise during running or on largely static effort during gymnastic exercise. During running, blood pressure rose up to 151/79 mm Hg, while gymnastic exercise gave mean values of up to 200/130 mm Hg as a result of sustained muscle contractions and forced breathing. Such uncontrolled maximal effort may be unexpectedly dangerous to persons with cardiovascular disease and fitness trails should not be recommended in the rehabilitation of cardiac patients.


[Influence of radio and television sets on implanted cardiac pacemakers (author's transl)]. Investigations done on implanted pacemakers with a low threshold against extraneous signals and in-vitro tests under suitable conditions both showed that pacemaker wearers may go near television and accessories such as ultrsound distant control or flexless infrared ear phones without any danger. Radio and television sets are fitted to an increasing degree with electronic sensor switches which initiate various functions after a slight touch. This satisfies present regulations of German Electrical Engineers concerning permitted contact currents. However, pacemaker patients can cause impulse defects by use of sensor switches provided the contact current is less than 25 muA. Sensor technique will in the future be introduced for everyday use on a large scale. Therefore, pacemaker patients should be alerted to the possibilities of an influence, and industry should be made to reduce contact currents in sensors to values below 20 muA.


[Collagen peptidase in Crohn's disease]. Collagen-peptidase activity in serum was increased in 54 of 71 cases of Crohn's disease. This increase was highly significant (P less than 0.001) compared with the results in a control group (24 cases). Immunosuppressive drugs (corticosteroids, azathioprine) decreased collagen-peptidase activity in the patients with Crohn's disease. On average it was higher than that of patients with sarcoidosis. Further tests are required to establish whether collagen-peptidase activity is of diagnostic value in Crohn's disease.


[Serological hepatitis B characteristics in clinical laboratory control sera]. 99 samples of 29 different reference sera were tested for HBs-antigen and anti-HBs radioimmunologically and by means of counter-current electrophoresis. 4 of 99 (4%) of the samples and 4 of 29 (14%) of the reference sera were HBs-antigen positive. 45 of 99 (45%) of the samples and 5 of 29 (17%) of the reference sera were anti-HBs positive. Reference sera are an additional risk for hepatitis in clinical laboratories and must be considered potentially infectious.


[Prevention of HBs antigen-positive serum hepatitis with hyperimmune-globulin anti-HBs]. Selection of donors to prevent HBs-antigen positive serum hepatitis has been only partially successful. For this reason the attempt was made to prevent the disease by passive immunisation with anti-HBs antibodies. A prerequisite for the systematic use of such immunisation is the determination of antibody threshold which would still provide protection. Plasma elimination of transmitted. HBs antibodies was serially measured in five children with terminal renal failure and ten normal subjects after intensive contact with HBs antibodies. Half-life values indicated marked individual variations which have to be taken into account with long-term prophylaxis. In the children they were 28.5, 25.9, 16.6, 11.7 and 7.8 days, respectively. In the healthy subjects the half-life averaged 20.3 days. The long-term programme developed by the authors appears to be suitable for revealing the value of hyperimmune-globulin anti-HBs in the prevention of HBs-antigen positive serum hepatitis.


[Frequency of chronic non-suppurative destructive cholangitis and primary biliary cirrhosis in comparison with other chronic inflammatory liver diseases]. Primary biliary liver disease was diagnosed and verified by histology and demonstration of antibodies against mitochondrial proteins in 73 patients between 1970 and 1974. Comparing cases between 1950 and 1961 and between 1970 and 1974 with the frequency of other chronic inflammatory liver diseases it was found that figures for advanced primary biliary cirrhosis remained unchanged during both periods whereas early stages of primary biliary disease were detected far more frequently in the latter period. One case with chronic non-suppurative destructive cholangitis or complete primary biliary cirrhosis was outnumbered by 8 cases of chronic aggressive hepatitis and 15 of liver cirrhosis of various aetiologies in Kassel. The relations in Göttingen were 1 : 5 and 1 : 6, respectively. Primary biliary diseases are no longer rare.


[Intrahepatic cholestasis due to N-propyl ajmaline]. In two patients intrahepatic cholestasis and cholestatic liver disease probably due to N-propyl ajmaline were observed. In both cases there was a four-week-interval between the first ingestion of the drug and the onset of jaundice. In one case with rigors there was a temporary rise in temperature and cholestasis. In the other there was a two to three week prodromal period of pruritus and gastro-intestinal symptoms. Both cases were characterised by blood and pronounced tissue eosinophilia in the periportal zones, a marked increase of cholestatic and hepatic cell enzymes, serum bilirubin and cholesterol, a moderate increase in erythrocyte sedimentation rate and absence of leucocytosis. Pathological laboratory findings returned to normal spontaneously within 5 weeks in one case and within two weeks under steroid therapy in the other.


[Differences in taste assessment of sweeteners by normal and overweight persons]. Taste assessment was tested in 20 obese and 20 normal-weight in-patients using watery solutions of saccharose and three synthetic sweeteners. Each patient was asked to assess ten different taste qualities of each solution on a point scale. There were highly significant differences between the two groups of subjects. The difference was especially marked for the categories "synthetic - natural", "unpleasant - very tasty", and "changeable - stable in times". These findings suggest changes in physical or central taste sensation in obese persons. This view is supported by their decreased ability to differentiate between saccharose and any sweetener. The results further support substituting sweetening agents for sugar in reducing diets.


[Coincidence of Hodgkin's disease and epithelioid-cell granulomatosis in liver and spleen]. Two of seventy patients with Hodgkin's disease who had exploratory laparotomy with liver biopsy and splenectomy were found to have extensive epithelioid-cell granulomas in liver and spleen. The coincidence of malignant tumour and epithelioid-cell granulomas of liver and spleen without lymph-node involvement is unusual. Knowing of the coincidence of Hodgkin's disease and such granulomas is clinically important because extensive diagnostic measures, including biopsy, are necessary in the differential diagnosis, and the patient's prognosis will depend on the therapeutic measures taken.


[Results of gastric lymphography with particular reference to gastric carcinoma (author's transl)]. The regional lymph nodes of the stomach can be visualised radiologically by injecting Lipiodol Ultra-Fluid into the submucous layer of the stomach wall through a gastroscope. Lymphography was performed in gastrologically healthy probands (n = 10), in patients with gastroduodenal ulceration (n = 17), and in patients with gastric carcinoma (n = 35). In 28 of the gastric carcinoma patients the first order lymph nodes were demonstrated, in 21 cases the second order and in 15 cases the third order whereas defects in uptake indicated metastases in 16 patients which could be histologically confirmed in 13. Gastric lymphography may contribute to the indication for operation if metastases are suspected in the second and third order lymph nodes as nodes along the upper border of the pancreas and the coeliac trunk are very difficult to remove radically.


[Clinical features and surgical treatment of carcinoma of the pancreas (author's transl)]. From 1964 to 1975 a total of 338 patients were operated on for pancreatic cancer. Duodenopancreatectomy was performed in 69 (20%), at a postoperative death rate of 16%. Second look operations proved to be worthwhile. Thus the resection rate after first operations elsewhere was 27%. Five patients lived for more than five and 19 for more than two years after operation. Since 1971 30 patients have survived so far after radiacal operation.


[Synovectomy in the prevention of recurrent joint bleedings in haemophilia (author's transl)]. Synovectomy was performed in seven patients with severe haemophilia A, one with moderately severe haemophilia A and one with severe haemophilia B. Frequently recurring haemorrhages into one knee and demonstrated hypertrophic synovitis were the indications for operation in all. No serious bleeding complications occurred during or after the operations. After synovectomy the frequency of haemarthroses in the synovectomised joint decreased significantly. Satisfactory joint function was eventually achieved in all by gymnastic exercises and physiotherapy over a long period. The operation should only be done in large haemophilia centres were there is sufficient experience.


[Transverse axial computerized tomography (EMI scan): value and indications (author's transl)]. The results of transverse axial computerized tomography in EMI scan (transverse CAT) in 2 000 examinations are reviewed. The method was shown to enlarge significantly the diagnostic possibilities in cerebral disease. A correct identification of intracranial tumour was made in 98% of 250 cases. Cerebral haemorrhage, infarction and contusional oedema could be differentiated. Various forms and extensions of cerebral oedema were visualized as never before. Postoperative changes and the course of vascular disease, tumour or hydrocephalus after shunt were demonstrated at an early stage. The indications for pneumo-encephalography have been reduced to a few very special situations. On the other hand, angiography is still of decisive value in vascular cerebral disease and should be performed before surgery in case of space-occupying lesions.


[The prodromal phase of myocardial infarction (author's transl)]. The prodromal phase was studied retrospectively in 101 patients who had sustained acute myocardial infarctions. Only in a few did the infarction occur suddenly. Prodromal symptoms occurred in 80%: angina pectoris of various forms, especially change in type of complaint, signs of heart failure and non-specific general symptoms. With approaching infarction, approximately from the third week onwards, there was a crescendo course of anginal symptoms and of heart failure. Especially typical was change in the form of the angina, with occurrence of spontaneous or resting angina or recumbent angina. Such anginal symptoms, without previous angina on effort, only occurred during the last seven days before the infarction. Angina with manifest or latent signs of heart failure in the course of increasing symptoms (crescendo course) was typical for the last three to four days before infarction. There was an increased incidence of prodromal signs in anterior-wall infarction. A crescendo course implied a worse prognosis. Prodromal symptoms are frequent and prognostically less favourable also in women.


[Results of cancer screening in women (author's transl)]. The results of cancer screening in women were evaluated from 1,1 million investigations during the third quarter of 1971 to the second quarter of 1974. Positive cytological results of the uterine cervix were found in 0,39% on first investigation and in 0,38% on repeat investigations. Positive results in the breast amounted only to a quarter (0,1%) of the frequency of positive cytological results despite the fact that breast cancer occurs more frequently than cervical carcinoma. Only 0,03% positive findings were obtained by digital rectal palpation. The low incidence of the diseases sought for and the partly low sensitivity of the screening methods are responsible for the small numbers of positive findings in early detection investigations and are an indication of the effort involved. Participation of the population in investigations for early detection of cancer is unsatisfactory especially in older age groups with an increased risk.


[Generalised herpes simplex virus infection presenting as an "acute abdomen" (author's transl)]. A 23-year-old patient developed acute upper abdominal symptoms during in-patient treatment for vulvo-vaginitis. Clinical picture, scintigraphy and angiography suggested a space-occupying process of the liver. Laparotomy showed ascites and a congested liver covered with cell necroses. The patient died the day after the operation from circulatory failure. Virological investigations of liver and spleen cell suspensions as well as the ascites fluid led to the demonstration of herpes virus type 2. The complement binding reaction gave a titre of 1:20 to herpes simplex virus. Disseminated herpes simplex virus infection is rare and in this case spread from the genital area.


Drugs and gastric damage.

Drugs and gastric damage. The effects of aspirin, salicylate formulations and substitutes, smoking (nicotine), indomethacin, corticosteroids, phenylbutazone, ethanol, caffeine and reserpine on the gastric mucosa are discussed. The damaging effects of the drugs are considered in terms of the gastric mucosal barrier, gastric  erosions, microbleeding and haematemesis and melaena and finally whether they cause peptic ulcer. There is suggestive evidence that unbuffered aspirin is a cause of haematemesis and melaena and of gastric ulcer but the incidence rates for hospital admission are low, being 10 to 15 per 100,000 heavy users per year. Aspirin in solution as acetylsalicylate buffered to maintain a neutral pH protects against gastric damage. Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated. Smoking is definitely associated with peptic ucler but the mechanism is unknown. Corticosteroids are probably not ulcerogenic despite clinical bias that they are. Indomethacin and phenylbutazone may be ulcerogenic but there is insufficient evidence to make firm judgements. Ethanol, caffeine and reserpine, on available evidence, are probably not ulcerogenic.


[Gerstmann's syndrome (critical review of the literature)]. Serious doubts have been casted upon the validity of the Gerstmann's syndrome since the paper of Benton in 1961. On the other hand, the results of several recent works suggest that it could not be a mere artifact. The analysis of this results, and mostly the theoretical works of Luria on the physiology of higher cortical functions, make it possible to imagine a functional unity behind the heterogenous signs of this syndrom, and the other manifestations of left parieto-occipital lesions. The data collected in the litterature are discussed, with special reference to the theoretical implications of Gerstmann's syndrome.


[Effect of psychotropic drugs on physiological variations and psychometric scores during attention]. A study was undertaken to determine the activation profile and psychometric performances in 10 adult volunteer subjects. The activation profile was evaluated by measuring heart and respiratory rates and also the H reflex (motor response). Psychometric performances during two attention tests were measured by the subjects' scores. The subjects were then submitted to a per os psychotrope drug treatment at a liminar therapeutic dose. Psychometric performances were decreased in subjects given a strong psychoactivator drug (amphetamine, genozolone), while they could be increased to an optimal level with a less active psycho-activation (Pyrisuccidéanol). Under the same conditions, the motor response, tested using the H-reflex, varied in the same way as the psychometric performance curve. However, the cardiac and respiratory rates show changes induced by the administered drugs. These results show some conditions were performance and activation are dissociated under the effect of psycho-active drugs.


Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Sequential blood samples were obtained from undisturbed freely-behaving male rats bearing chronic intracardiac venous cannulae. Blood was withdrawn every 15 min for periods of 4-24 h; plasma was separated, and saline-resuspended red cells were reinjected. Plasma GH was determined by radioimmunoassay. Pulsatile GH secretion was evident in each animal with most peak values greater than 200 ng/ml and most trough values less than ng/ml. The GH secretory episodes occurred at approximately 3 h intervals, and this rhythmic pattern of GH secretion persisted unchanged across all phases of a 12-h light-dark (L-D) cycle. Seven major episodes of GH secretion were observed during a single 24-h period. The mean period, or time interval between episodes, in 24 animals was 3.32 +/- 0.07 (SEM)h. The timing of the pulses with respect to the L-D cycle was similar in most animals, indicating that the rhythm may be entrained to the L-D cycle. The role of environmental lighting was further assessed in 14 animals exposed to constant light for 7 weeks. The results show that the basic rhythm was unchanged (mean period 3.18 +/- 0.06 h, peaks greater than 200 ng/ml, troughs less than 1 ng/ml), although entrainment to time of day was not evident. Subsequent exposure to the 12-h L-D cycle resulted in reversion to an entrained rhythm. These results suggest 1) that GH secretion in the rat is governed by an endogenous ultradian rhythm, with a periodicity of approximately 3.3 h, and 2) that the alternation of light and darkness probably serves as a Zeitgeber which sets the biological "clock" for GH secretion, but is not necessary for maintenance of the basic rhythm.


Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats. Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance.


Effect of the ergot derivative lisuride hydrogen maleate on serum prolactin concentrations in female rats. The influence of a new synthetic ergot derivative, lisuride hydrogen maleate (LHM) on serum prolactin (PRL) concentrations was investigated in female rats using different test models: 1. in reserpine (R)-pretreated intact females, and 2. in ovariectomized (OVX) estradiol benzoate (E2)-primed animals with or without an additional pretreatment with R. In all the models used LHM was strongly effective in lowering serum PRL. Doses from 0.025 to 0.5 mg/kg LHM, given orally as well as subcutaneously, suppressed serum PRL. Depending on the dose used, the serum PRL was lowered to a different extent for up to 12 h. LHM was at least as effective as the well-known potent inhibitor of PRL secretion CB-154 in lowering serum PRL in OVX rats primed with E2. The effects of R, E2, and LHM are described in relation to their mode of action within the hypothalamic-hypophyseal system which regulates PRL secretion. While the increase in serum PRL induced by R seems to be directly relatable to its known catecholamine depletion, the circadian rhythm of PRL secretion induced by E2 seems to be influenced or mediated by central neural mechanisms. The effects of LHM on serum PRL in these test models can be related to its dopaminergic action and constitute further evidence for the central functions of dopaminergic mechanisms in the regulation of PRL secretion.


Comparison of somatomedin activity in perfusates of normal and hypophysectomized rat livers with and without added growth hormone. We compared the somatomedin (SM) activity of perfusates of livers from normal and hypophysectomized (hypox) rats with and without the addition of growth hormone (GH) to the perfusions. Livers were perfused for a total of 3 hours, with a change of Waymouth's medium MB 752/l every 30 min, in a continously recirculating system. SM activity was estimated by the stimulation of the incorporation of sulfate by hypox rat costal cartilage incubated in vitro. Endogenous SM activity (no addition of GH) in the perfusates of the livers of normal rats was initially 136 +/- 17% above buffer levels (mean +/- SE) and fell gradually to near-buffer levels over the first 2 1/2 hours. Endogenous SM activity in the perfusates of livers from hypox rats was initially 72 +/- 10% above buffer levels, significantly lower than that of the normal livers, and reached buffer levels with the fifth medium change. Pretreatment of hypox rats with GH in vivo increased their initial liver perfusate SM activity to 134 +/- 25%, comparable to that of normal livers and significantly greater than that of livers of untreated hypox rats. The addition of GH (25 mug/ml) to the perfusion of both normal and hypox rat livers led to significant increases in perfusate SM activity compared with that of control perfusates at the same time periods. The increase in SM activity was not significant until after 0-30 minutes with hypox livers, and after 30-90 minutes with normal livers. Although it has previously been reported that the direct addition of GH to livers perfusion systems led to an increase in perfusate SM activity, we have now established that in the absence of added GH, perfusates of normal rat livers contain significant SM activity, and that perfusates of normal rat livers contain more SM activity than perfusates of hypox rat livers. In addition, the observation that GH pretreatment increases the SM activity of perfusates of hypox rat livers constitutes the first evidence that SM activity of any body tissue may be altered by administration of GH in vivo.


Antibodies to catecholamines.

Antibodies to catecholamines. The haptens p-tyramine and synephrine were conjugated to bovine serum albumin by means of the formaldehyde condensation reaction. These conjugates were emulsified in adjuvant and injected into rabbits. Antiserum was harvested at 10-day intervals after booster injections. The anti-sera were screened by immunodiffusion. After detecting the presence of antibody, an antiserum was further characterized by antiserum dilution curves, standard curves, and cross-reactivity studies using labeled p-tyramine or labeled metanephrine. The cross-reactivity studies indicated that the antisera to either hapten had low affinity to compounds with structural deviations on the side chain or ring other than at the position ortho to the phenolic hydroxyl group. The antisera were more sensitive to 3-methyoxylated compounds (3-methody-tyramine and metanephrine) than to 3-hydroxy or unsubstituted compounds.


Prepuberal estrogen treatment and somatic growth in rats. Male and female rats receiving estradiol from weanling to early adulthood displayed a reduction in body weight gain and skeletal growth over the entire treatment period. At 76 days of age exogenous estrogen was discontinued and bilateral ovariectomies were performed on the females. The 17-week posthormone period was characterized by an accelerated rate of growth of both sexes; however, only the male rats had posthormone growth rates that indicated total compensation for the early depressant effects of estrogen. These results argue against recent proposals suggesting that mechanisms regulating the body weight and growth of rats are insensitive to estrogen until the onset of natural puberty. It is not clear from the present work what mechanism is responsible for the reduced growth. However, the similarities of the somatic growth effects of estradiol, as noted here, and the effects of undernutrition on young rats suggest that hypophagia may cause the depression of growth noted during estrogen treatment.


Comparison of the delayed actions of growth hormone and somatomedin on adipose tissue metabolism. Although acute insulin-like effects of growth hormone (GH) on adipose tissue are readily demonstrable in vitro, it has not been possible to reproduce in vitro the delayed (3 h) inhibition of glucose utilization seen after the administration of GH in vivo. To examine the possibility that somatomedin (Sm), the postulated mediator of GH action, might, like GH, have biphasic effects on adipose tissue metabolism and mediate the delayed inhibition of glucose utilization, Sm was prepared by gel filtration from an acid-ethanol extract of normal rat plasma. The partially purified material increased 35SO4 incorporation into costal cartilage of hypophysectomized rats and produced in adipose tissue an acute stimulation of glucose oxidation that was not suppressed by insulin anti-serum. Unlike GH, whose insulin-like effects disappear in 3--4 hours, Sm-stimulated glucose oxidation remained linear for the entire 4 hour incubation period. Although acute stimulation of tissues with GH rendered them refractory to renewed insulin-like stimulation by GH, no such refractoriness to the action of Sm was seen. Furthermore, acute stimulation with Sm failed to render tissues refractory either to itself or to GH. Finally, Sm failed to reproduce the delayed lipolytic effects produced by GH in conjunction with glucocorticoids. These results make it highly unlikely that Sm alone accounts for the delayed metabolic effects of GH.


Lack of effect of various endocrine manipulations on tryptophan hydroxylase activity of individual nuclei of the hypothalamus, limbic system, and midbrain of the rat. The tryptophan hydroxylase activity of individual nuclei of the limbic system, hypothalamus, and midbrain was determined after various endocrine manipulations in an attempt to identify specific endocrine-responsive serotonergic structures in the rat brain. Following adrenalectomy, thyroidectomy, castration, or treatment with pharmacological doses of dexamethasone, testosterone, or thyroxine, no changes in tryptophan hydroxylase activity occurred in any of the areas of brain examined. Furthermore, in large sections of the hypothalamus and midbrain, total tryptophan hydroxylase activity was unaltered, and no changes in Km for substrate or co-factor were found after adrenalectomy. This study, therefore, has failed to detect any hormonally responsive tryptophan hydroxylase activity in the rat brain. These findings suggest that endocrine-induced alterations in serotonin turnover, if they occur, do so without measurable changes in the activity or kinetic properties of tryptophan hydroxylase.


Mammary blood flow and endocrine changes during parturition in the ewe. The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition.


Differential effects of L-thyroxine on cardiac and hepatic monoamine oxidase activity toward benzylamine and serotonin. Male and female rats of 2 age groups were given subcutaneous injections of L-thyroxine (500 mug/kg) at 12 h intervals for a period of 10 days. The activity of monoamine oxidase (MAO) in normal and thyrotoxic rats was studied with two substrates: benzylamine and serotonin. The results showed that a thyroxine effect on cardiac and liver MAO activity is dependent on the substrate used in the assay. Kinetic studies of cardiac and liver MAO after thyroxine-treatment showed an unaltered Km for benzylamine but a change in Km for serotonin. Both findings may indicate a discriminative action of thyroid hormones on different forms of MAO. The possible presence of a soluble activator and inhibitor for MAO was investigated.


Isolation and characterization of follicle-stimulating hormone and luteinizing hormone and its subunits from snapping turtle (Chelydra serpentina) pituitaries. Highly purified luteinizing hormone and follicle-stimulating hormone have been isolated from extracts of snapping turtle (Chelydra serpentina) pituitaries. Both hormones are potent in non-mammalian gonadotropin bioassays (1.8 X NIH-LH-S1 and 30 X NIH-FSH-S1). The materials have been characterized by polyacrylamide gel electrophoresis, amino terminal group analysis, amino acid and carbohydrate content, and, in the case of turtle luteinizing hormone, ultracentrifugation. The luteinizing hormone was shown to dissociate and subunits were prepared by the countercurrent distribution technique and characterized. Biological activity of the hormone could be regenerated by recombination of the subunits. In addition, it was shown that the snapping turtle luteinizing hormone subunits could be combined with subunits from ovine luteinizing hormone with generation of significant biological activity. Comparisons in properties of the turtle gonadotropins have been made with ovine gonadotropins, showing, in many cases, similarities in properties, suggesting structural features which have been conserved during evolution.


Differentiation between neural and hormonal control of sexual behavior and gonadotropin secretion in the female rat. The purpose of this study was to assess the relative roles of the neural and endocrine feed-back systems in the regulation of gonadotropin secretion and behavior in the female rat. Retrochiasmatic knife cuts were placed in animals which were tested for mating behavior on five consecutive days, subsequent to the development of cornified vaginal smears. A knife-cut control group was autopsied immediately after behavioral tests. A second knife-cut group and a group of cycling controls were acutely ovariectomized, and their behavior was assessed until mating ceased. Some of each of the two groups were administered small daily amounts of estradiol cypionate (estrogen) under two-dose regimens. Mating behavior and vaginal cytology were followed, and autopsies were performed 70 days after ovariectomy. At autopsy, serum was collected for LH, FSH, estradiol, and progesterone radioimmunoassays. The knife cuts caused high levels of mating on five consecutive days of testing in all animals. After ovariectomy, the surgical group mated at higher rates for longer time periods than did the controls, and the vaginal smears were predominately leukocytic. Knife cut controls had significantly elevated serum estrogen titers over cycling controls except for proestrous morning values. Exogenous estrogen was retained longer in the serum in the surgical than in the control group. Progesterone was relatively low in the retrochiasmatic cut groups. Serum LH was not elevated in the surgical groups except following ovariectomy; exogenous estrogen not only stimulated more mating sooner in the surgical group, but inhibited high levels of LH caused by ovariectomy. FSH was elevated in the surgical and control ovariectomized groups, and exogenous estrogen lowered FSH in the surgical but not the control group. Estrogen and LH levels were compared between the control and knife cut groups, and it was determined that the set-point for negative feedback effects of estrogen on LH was comparable for the two groups. It was concluded that retrochiasmatic knife cuts cause high estrogen titers, which may be responsible for the continuous behavior in animals with intact ovaries, whereas, in the absence of ovaries, the surgical treatment may reduce fore-brain inhibition on behavior. The data also suggest that the mediobasal hypothalamus in animals with retrochiasmatic knife cuts responds normally to exogenous estrogen by reducing LH secretion in the ovariectomized animal.


1,25-Dihydroxycholecalciferol effect on serum phosphorus homeostasis in rats. It has recently been shown that 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) increases the serum phosphorus concentration of rats on a low-phosphorus diet. While studying the biological activity of 1,25(OH)2D3, we observed that under certain circumstances 1,25-(OH)2D3 would decrease the serum phosphorus concentration. The analysis of all data obtained in rat experiments during the past 3 years revealed highly significant linear correlations (P less than 0.001) between changes of serum phosphorus concentrations after the administration of 1,25-(OH)2-D3 (130 pmol/d for 1 or 5 days) and serum phosphorus or calcium levels in the animals before injection. Similar correlations could only be found with the higher dose of 25-hydroxycholecalciferol (130 pmol/d for 5 days). Another vitamin D3 metabolite, 24,25-dihydroxycholecalciferol, had no effect on serum phosphorus concentrations under our experimental conditions. The 1,25-(OH)2D3 effect on serum phosphorus concentration does not require the presence of circulating parathormone and/or calcitonin. We suggest that 1,25-(OH)2D3 might be an important factor in serum phosphorus homeostasis.


Gap junctions in thyroid epithelium of the rat. Gap junctions were observed on the lateral plasma membrane of the typical thyroid epithelial cell in freeze-fracture preparations of rat thyroid gland. The gap junctions were 0.1 to 0.4 mum in diameter and were composed of closely packed, approximately 80 nm particles. They were located from 1 to 6 mum from the apical surface of the cell.


A granule-associated L-thyroxine deiodinating system in the human leukocyte. Recent work has shown that leukocytes deiodinate L-thyroxine (T4) and that deiodination is enhanced when phagocytosis is induced. To define the subcellular locus and characteristics of this phenomenon, the deiodinative activities of different cell fractions obtained from human leukocytes (greater than 90% polymorphonuclear) were studied. Of the several fractions obtained, the granule fraction was found to possess the bulk of T4-deiodinative activity; as little as 9 mug/ml of granule protein effected significant deiodination of added labeled T4. Prior exposure of intact leukocytes to opsonized zymosan particles to induce phagocytosis resulted in an increase in the T4-deiodinative activity of the subsequently isolated granule fraction alone, strengthening the validity of the finding that T4-deiodinative activity in the human leukocyte resides in the granule fraction. The characteristics of the granule-associated deiodinating system suggest that it is enzymic in nature with a Km of the order of 10(-6)M.


Direct calcium-stimulated release of glucagon from the isolation perfused rat pancreas and the effect of chemical sympathectomy. "Staircase" increments of calcium (from 0.5 to 15 mEq/L) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large calcium concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the calcium-induced glucagon release at the lower calcium steps. The response to a subsequent stimulation by arginine/calcium was not inhibited. Results suggest that glucagon secretion is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and that calcium in part positively affects release by permitting this neural stimulation.


Effects of neurotensin and substance P on plasma insulin, glucagon and glucose levels. Neurotensin and substance P given iv 5, 10, 20 and 30 minutes prior to blood collection produce hypoinsulinemia, hyperglucagonemia and hyperglycemia in the rat. Glucagon similarly produces hyperglycemia in rats but results in hyperinsulinemia. On a molar basis neurotensin is ca. 10 and 30 times more active in inducing hyperglycemia than substance P and glucagon, respectively. The enhanced glucogenic effects of neurotensin and substance P over glucagon may well result from their inhibition of insulin release. Neurotensin and substance P may be important in glucose homeostasis.


Demonstration of specific binding of prolactin by porcine corpora lutea. Subcellular fractions from porcine corpora lutea of the reproductive cycle and pregnancy were shown to have specific binding sites for ovine prolactin (oPRL). Aside from oPRL, only ovine and bovine growth hormone preparations competed with [125I]iodo-oPRL for its binding site. These cross reactions were at a level consistent with the prolactin contamination of these preparations. Rat growth hormone, FSH, LH, TSH, insulin, and ACTH exhibited negligible cross-reactivity. Both corpora hemorrhagica and albicantia had lower specific binding of [125I]iodoPRL than did active corpora lutea of the reproductive cycle, while corpora lutea of pregnancy demonstrated a nearly 5-fold increase in specific binding compared with that of the cycle. Corpora lutea from animals with larger fetuses (greater gestational age) bound the most prolactin. Analysis of data from cold competition studies employing weighted non-linear least-square fitting to a three-parameter model, showed high-affinity binding of oPRL with an association constant (Ka, 23 C) of 2.0 X 10(9)M-1 for the binding site of the corpus luteum of the cycle. The Ka shows no appreciable change with pregnancy. In contrast, the binding site concentration (N) increases markedly from less than 10 fmol/mg protein in corpora lutea from non-pregnant animals to approximately 40 fmol/mg protein for animals at a gestational stage of 40-46 days. The observed Ka's are similar to values obtained for the prolactin binding site in porcine granulosa cells harvested from unruptured follicles and to the prolactin-binding site in the mammary gland.


Differential effects of male stimuli on follicle-stimulating hormone, luteinizing hormone, and prolactin secretion in prepubertal female mice. Puberty may be induced rapidly in young female mice by exposing them to adult males. The relevant male stimuli include a urinary pheromone and tactile cues, the latter acting in a potentiating capacity. The specific action of the urinary pheromone on pituitary gonadotropins was the subject of the present research. Immature females of a standard size were either paired with adult males, isolated and their bedding sprayed with male urine, or maintained as isolated controls. Exposure to male urine resulted in a rapid and significant release of LH (30 min) which was maintained at an average of 50% higher than levels in isolated controls throughout the 48 h experiment; no immediate changes were observed in either serum FSH or prolactin, but FSH was depressed and prolactin rose progressively during later sampling periods. Cohabitation with an adult male yielded parallel but decidedly stronger reponses in the concentrations of all three hormones. Exogenous estrogen, administered in a second experiment at a dosage previously found to mimic the puberty-inducing action of a male, suppressed serum FSH and LH while elevating serum prolactin. Thus, the present results suggest a) that the male's urinary stimulus exerts its action on immature females via LH release with no immediate and/or direct effects on the other two tropic hormones, and b) that the delayed alterations in serum FSH and prolactin concentrations accompanying male- and/or urine-exposure are secondary consequences of an LH-induced release of estradiol. Attempts to induce the entire pubertal cycle in intact females with subovulating doses of LH, nevertheless, were unsuccessful.


Abnormal thyroid function in spontaneously hypertensive rats. Thyroid weight, thyroidal radioiodide uptake, and cyclic AMP-dependent protein kinase activity of a thyroid supernatant fraction were increased significantly in spontaneously hypertensive rats (SHR), apparently because of increased secretion of pituitary TSH. However, the thyroids of SHR did not make supernormal amounts of thyroxine (T4), and thyroidal radioiodine release was apparently impaired. In the SHR, proteolytic enzyme activity was less than normal and the thyroglobulin was more resistant to normal proteolytic enzyme than was control thyroglobulin. Presumably because of these abnormalities, plasma T4 was significantly lower than normal, but triiodothyronine (T4) was normal, as a result of compensatory processes occurring in T3 synthesis and hydrolysis of thyroglobulin. T4 and T3 were less effective in depressing pituitary TSH synthesis and secretion in SHR than in controls, possibly because of an abnormal setting of the "hormostat." Although the hypothalamic content of TRH was normal in SHR, the exact site of the abnormality in the "hormostat" is not delineated in the present study.


Growth hormone in encephalectomized rat fetuses, with comments on the effects of anesthetics. Plasma and pituitary immunoreactive growth hormone (GH) was measured in 21.5-day-old rat fetuses under various experimental conditions. Encephalectomy on day 19.5 was used as a method for depriving the fetus of its hypothalamus. The fetuses were recovered on day 21.5 under maternal pentobarbital anesthesia. Total encephalectomy or partial encephalectomy (ablation of superficial brain structures) similarly affected fetal growth. The mean GH contents of the pituitaries were not significantly different in the four groups of fetuses studied: controls from intact females (1.38 +/- 0.19 mug/gland), controls from females submitted to surgery on day 19 (1.47 +/- 0.13 mug/gland), surgically encephalectomized fetuses (1.13 +/- 0.12 mug/gland), sham-operated fetuses (1.19 +/- 0.10 mug/gland). The mean plasma GH levels were the same in control fetuses of intact females (147 +/- 8 ng/ml) and in control fetuses of females submitted to surgery (168 +/- 9 ng/ml). The values were lower in sham-operated fetuses (118 +/- 11 ng/ml) and considerably reduced (P less than 0.001) in encephalectomized fetuses (60 +/- 8 ng/ml). Plasma GH was higher in the fetuses of females killed less than 2 min earlier, than in the fetuses of anesthetized females. In dams anesthetized with pentobarbital or ether, the fetal plasma levels of GH were not different after 15 or 45 min of maternal anesthesia. Under maternal urethane anesthesia, the fetal plasma GH was at 15 min significantly lower than it was under (P less than 0.01) or pentobarbital (P less than 0.05); 30 min later, it had increased by 40% (P less than 0.025). It appears that the release of GH in the fetus can be modified by anesthetics, and that some GH still is released by the pituitary gland in the absence of the hypothalamus.