Multiple sensitivity to chemical stimuli in single human taste papillae.

The sensitivities of 15 human fungiform papillae were tested using a 5-alternative forced-choice procedure. Subjects were aked to recognize which of the following stimuli was presented to a papilla on each of 250 trials: 5.0 M NaCl, 0.5 N citric acid, 1.0  M quinine hydrochloride, and distilled H2O. Solution droplets were delivered to individual papillae from 0.5 mm diameter platinum wire loops. Based on each subject's responses to distilled H2O, corrections were made for individual response biases. Of the papillae tested, 33 percent responded to all four compounds, 33 percent to three, none to only two, 20 percent to only one, and 13 percent to none of the chemical stimuli.  These results are contradictory to earlier work, in which it was suggested that taste quality is encoded by chemically specific papillae, but are consistent with the electrophysiological data suggesting multiple sensitivity of mammalian gustatory receptor cells and first-order neurons. The data suggested that the narrow range of sensitivity reported by von Békésy [2] was determined by the reciprocal relationship between the size of the stimulated area and the concentration necessary to elicit a threshold sensation.


Differential effects of cortical ablation and spreading depression on sensitivity to footshock: implications for the role of the cortex in learning.

Rats were tested for flinch and jump responses to shock under unilateral and bilateral spreading depression (USD and BSD) and unilateral cortical ablation (UCA). Some Ss were tested with insulating boots on the left or right limbs. Under USD and  UCA the limbs contralateral to the depressed or ablated hemisphere were as insensitive as when under BSD, and the ipsilateral limbs were almost as sensitive as in the normal condition. The data indicate that lack of transfer typically found in the USD transfer paradigm can be attributed to stimulus factors and not to learning or memory deficits, especially since most studies have used a shock level which does not exceed the jump threshold for a depressed hemisphere.


The nature of the thirst stimulus: a factor in conditioned taste-aversion behavior.

Independent groups of rats were compared drinking in response to either water deprivation or osmotic thirst induced by intraperitoneal injections of hypertonic saline. When water or a palatable saccharin solution served as the drinking fluid, deprivation and osmotic thirst produced comparable fluid intakes. In contrast, when a saccharin solution previously associated with the aversive effects of lithium served as the drinking fluid, animals injected with hypertonic saline drank substantially less than water deprived animals. Experiment 2 indicated that this hyperreactivity to a conditioned aversive flavor in animals suffering from osmotic thirst was due to the reduced palatability of the saccharin flavor rather than the previous experience with lithium. Experiment 3 showed that the effect also could not be attributed to differential taste-aversion learning, handling, food deprivation or weight loss before the test sessions. The phenomenon is discussed in terms of various differences between thirst induced by water deprivation and thirst induced by acute cellular dehydration.


Renal deficiency associated with diabetes insipidus in the SWR/J mouse.

The age-dependent polydipsia and polyuria observed in SWR/J mice was found to be caused by relative inability of the kidneys to respond to antidiuretic hormone (ADH), resulting in a concentrating defect, which persisted even following Pitressin injection or water  deprivation. Posterior pituitaries contained large amounts of ADH, which was also found in the urine and increased in output following water deprivation, indicating normal, or above normal synthesis and release of ADH. Kidneys of polydipsic SWR/J mice weighed more than those of normal strains and sometimes contained a lesion in the medullary area. No clear relationship was found between the size of the lesion and water intake.


Regulatory drinking in rats with permanent access to a bitter fluid source.

Male rats were given a quinine adulterated fluid as their sole source of liquid for over 60 days. After a latency of a few days, fluid intake stabilised at about 20 ml/day, with the water to food ratio close to 1.0 ml/g. Bodyweights fell to 90 percent of control levels (rats drinking unadulterated water). A battery of dipsogenic challenges was administered. Compared to controls, the ingestive responses during elevated ambient temperature, hyperosmotic salty food, after fluid deprivation, and to extracellular fluid depletion, were all attentuated. Drinking to acute NaCl injections was totally abolished. The intake of the adulterated fluid was near zero during food deprivation, and when a vegetable and fruit diet was available. Body fluid changes were suggestive of a net dehydration in the quinine drinking rats. Parallels with self intravenous drinking rats and rats recovered from lateral hypothalamic lesions were  considered, and possible fundamental differences between natural and nonatural thirst stimuli.


Gonadectomy and the development of age-dependent polydipsia and the intake of NaCl solutions in the SWR/J mouse.

Gonadectomies were performed at 25 days of life in SWR/J mice, a strain known to develop age-dependent nephrogenic diabetes insipidus with females drinking far more than males. Effect of gonadectomy was different for each of the 3 nonreproductive behaviors studied. (1) Ovariectomy reduced the age-dependent polydipsia seen in females, but castration was without effect in males. (2) Castration of males resulted in a lower intake of an isotonic NaCl solution, making the castrated males similar to the sham-operated and ovariectomized females which did not differ. (3) For the short-term activity measurement sham-operated males did not differ from sham-operated females and castrated males did not differ from ovariectomized females. In each sex, gonadectomy reduced activity.


Genetic analysis of water maze discrimination learning for Mus musculus: polygenes and albinism.

Recombinant inbred strains, their progenitor strains and reciprocal F1 hybrids were given thirty spatial discrimination learning trials in the water maze. The pattern of RI strains in relation to the reciprocal F1 hybrids and the  progenitor strains, and differences among strains, suggested that different sets of genes affect the various components of water maze discrimination learning. There was no evidence that the albino gene influenced either inferior or superior performance. Pigmented strains performed as well as, or better than, some albino strains, and albino strain BALB/cBy differed significantly from albino strains CXBG and CXBI. The two reciprocal F1 hybrids differed from blocks 2 and 3 of discrimination trials when swimming time was used a  dependent variable. Thus, it appears that performance of the F1 hybrids was influenced by paternal effects, maternal effects, or paternal maternal interactions.


Effects of anti-estrogens on testosterone stimulated male sexual behavior and peripheral target tissues in the castrate male rat.

In the first experiment castrated male rats were injected daily with either vehicle or 800 mug testosterone together with either 6 hr pretreatment or concurrent treatment with the anti-estrogens CI-628 (4 mg) or MER-25 (20 mg). The only treatment found to significantly reduce male copulatory behavior was concurrent treatment with CI-628. Anti-estrogen treatment was also found to slightly reduce body weights, increase seminal vesicle weights in response to testosterone and to have no significant effects on androgen stimulated increases in penis weight and length. In the second experiment castrated male rats were injected daily with either vehicle or 500 mug testosterone together with 2.5 mg injections of CI-628 given 6 hr before and concurrent with the androgen injections. The anti-estrogen treatment was found to markedly inhibit the desplay of male sexual behavior, to reduce body weights, and to stimulate seminal vesicle weights. Penile weights and lengths were again not effected by the anti-estrogen therapy. These results were interpreted as supporting the theory that testosterone stimulated male sexual behavior in the rat following its aromatization to estradiol in the brain.


Locomotor, avoidance and maze behavior in rats with the dorsal fornix transected.

Transection of the dorsal fornix bundle in rats resulted in impaired maze learning, while the behavior in open field, passive avoidance and spontaneous alternation test was unchanged.  The results are discussed in  terms of an association deficit. It is concluded that the dorsal fornix is probably not to be regarded as part of the hippocampal output system.


Intranasal trigeminal detection of chemical vapors by humans.

The majorityof 14 human observers lacking olfactory nerve function detected, by nasal inhalation, over one quarter of 31 chemicals commonly used in olfactory research. No major differences were noted between anosmic observers with and without documented anatomic, genetic, or physiologic  etiology. Detected compounds differed significantly from nondetected ones on the basis of a number of chemical properties, including water solubility and molecular weight. Detection thresholds of  the anosmics, established by a single staircase procedure, were approximately two log volume concentration steps above those of normals for two compounds examined. Exponents of power functions fitted to magnitude estimates of the anosmics did not differ significantly from those fitted to the estimates of matched normal controls. These data indicate the trigeminal nerve may play an important role in human nasal chemoreception and that effective trigeminal stimulants may be predictable on physicochemical grounds.


Hypothalamic hyperphagia despite imposed diurnal or nocturnal feeding and drinking rhythms.

Rats normally do most of their eating at night. When ad lib fed rats are made hyperphagic with lesions or parasagittal hypothalamic knife cuts the increases in eating occur primarily during the day. This suggests that a disruption of circadian rhythms may mediate the overeating. However, when knife cut rats were food and water deprived all day excessive eating occurred at night. Similarly, when they were deprived all night overeating occurred during the day. Under both conditions  od deprivation the food intakes and rapid weight gains of the ad lib fed knife cut group were defended. It was concluded that: (1) in hypothalamic hyperphagia either the excessive food intake or the excessive weight gain is defended when food and water are available only half of each day, and (2) disruption of nocturnal feeding and drinking rhythms is not the cause of hypothalamic hyperhagia.


Anatomical asymmetry of the cerebral hemispheres of the cat brain.

The fissure patterns of 39 cat brains were examined and each hemisphere was classified according to the scheme of Otsuka and Hassier. Of the 33 brains for which there was no ambiguity of classification for either hemisphere, 45 percent were asymmetrical. Included among these asymmetrical brains was that of a newborn kitten.  As the asymmetry is focussed predominantly in the region of the visual cortex, it is suggested that this may form the substrate of the functional asymmetry in visual discrimination performance previously demonstrated in cats.


Dissociation  of operant and consummatory responses by trigeminal deafferentation in the pigeon.

Section of peripheral sensory branches of  the pigeon's trigeminal nerve abolishes or decreases feeding responses made in an operant conditioning situation without directly impairing performance of an operant key-pecking response reinforced with food. The results are discussed in relation to previous studies of trigeminal function in the pigeon and suggest the possibility of dissociating neural mechanisms underlying feeding behavior and operant conditioning in this species.


Mediodorsal nucleus and behavior regulation in the rat.

Twelve electrodes aimed at the mediodorsal thalamic nucleus were implanted in 6 rats. In 5 of these animals intracranial stimulation was effective in punishing a bar press response on a baseline schedule of water reinforcement. The sixth animal was not tested. In all 6 animals lesions produced through these electrodes disrupted  response suppression to punishing electric shock superimposed on the same baseline. Those animals in which both parts of the mediodorsal thalamic nucleus were damaged showed a more marked and graded punishment effect of intracranial stimulation and a more profound disruption of the quantitative shock intensity-response relationship than those in which only the rostromedial part of the nucleus was damaged.  Three other animals had electrodes implanted in the rostromedial hypothalamus or the midline thalamus. They showed neither the punishing effect of intracranial stimulation nor the dusruptive effect on response suppression of electrocoagulative lesions.


Elevated blood glucose levels and satiety in the rat.

Thirteen rats were placed on a feeding schedule of two 3 hr periods of food availability daily. blood glucose levels of the experimental animals were altered by intraperitoneal injection of 8 ml of 2, 5, 8, 12, 16, 20 and 25 percent glucose solutions and by intragastric loading of 8 ml of 25, 50 and 65 percent glucose solutions in 10 different feeding experiments. In 4 additional experiments, experimental animals received intraperitoneal injections of 8 ml of 12, 16, 20 and 25 percent solutions of mannitol, a non-metabolizable sugar-alcohol. Controls always received identical quantities of mammalian Ringer's solution administered via the same route as in the experimentals. Another set of 20 rats was used to determine glucose tolerance curves for each concentration of glucose and mannitol administered. No food intake depression occurred following intraperitoneal injections of 2, 5, 8 and 12 percent glucose, 12 percent mannitol and following intragastric loading of 25, 50 and 65 percent glucose. However, intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol caused depression of food intake. No depression of food intake occurred following intragastric loading of 50 and 65 percent glucose solutions which raised blood glucose levels a minimum of 43 mg percent and 55 mg percent above basal, respectively, for the duration of the 3 hr feeding period. These minimum blood glucose levels greatly exceed normal values following a meal. It was concluded that blood glucose level per se is not an important feedback parameter in the long-term control of food intake, and the depression in food intake following intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol solutions was due to an abnormal physiological condition.


Effect of gonadectomy on taste preference for glucose solutions in rats.

Mature male and female rats maintained on an ad lib diet were given a choice between tap water and glucose solutions of different concentrations (1, 5 and 12 percent). Both sexes exhibited a definite preference for the 12 percent glucose solution, but the females drank significantly more than males. Gonadectomy produced neither quantitative nor qualitative changes in the choice made by male rats. On the contrary, gonadectomized females showed a depression of the 12 percent glucose solution intake and an increase in the 5 percent glucose solution intake, resulting in a decrease of the total fluid intake. A comparison of ovariectomized and intact female rats in regard to the self-selection of tap water and a 5 percent glucose solution confirmed the stimulatory effect of ovariectomy on the 5 percent glucose solution intake. When a choice between tap water and 12 percent glucose solution was permitted the ovariectomized rats showed a weaker positive response to the sweet solution than the intact female rats.


Omission training and extinction in rats with septal damage.

Rats with either control operations or septal damage were pretrained on a VI 30-sec schedule and tested for response suppression ability on either an omission training (OT) task or on extinction. Septal damage enhanced barpressing on the VI 30-sec task. Animals with septal damage took longer to suppress responding on the OT task than controls while lesioned and control animals tested on extinction did not differ. Increased emotionality was seen in subjects with septal damage on the first test day but not thereafter. Animals tested with OT suppressed responding more rapidly than animals tested on extinction.


Graded acquisition of an instrumental avoidance response by the spinal rat.

Eight pairs of spinal rats were exposed to an instrumental conditioning paradigm in which one animal served as the experimental and the other as a yoked control animal. An electrode, inserted into the experimental animal's foot, contacted an aqueous solution delivering shock to both animals. Leg flexion terminated the shock. Following two consecutive min without shock, the experimental animal's solution was raised an additional millimeter and training was re-instated. This procedure was repeated 4 times, or until the experimental animal failed to reach the 2 min criterion. In Run 1, one leg was trained; during Run 2, the contralateral leg was used. In addition, the animal which served as the experimental in Run 1 served as the yoked control in Run 2 and vice versa. The results indicate that the spinal rat is capable of acquiring successively higher criteria in an instrumental conditioning routine. In conjunction with previous results, these findings suggest that instrumental avoidance learning can occur in the spinal cord.


Post-ejaculatory vocalization in castrated rats treated with various steroids.

Five groups of rats were observed for sexual behavior as intact subjects and in the 3 weeks following castration. Particular emphasis was placed upon ultrasonic vocalization recorded during the refractory period (RP) following ejaculation. All rats received daily injections (100 mug test steroid + 100 mug dihydrotestosterone propionate, DHTP) from the day of castration. Treatment groups were: Testosterone propionate (TP) + DHTP, N = 5; 19-hydroxytestosterone propionate (19HTP) + DHTP, N = 6; Oestradiol dipropionate (OP) + DHTP, N = 5; DHTP (200 mug/day), N = 6; Vehicle only, N = 7. Ejaculation and normal RPs were maintained with TP, 19HTP and OP treatments. In rats treated with DHTP alone or vehicle only ejaculatory ability declined and RPs increased in length. Ultrasonic vocalization was normal in all rats except those treated with OP, where it was either reduced or absent. In Week 4 treatments in TP + DHTP and OP + DHTP groups were reversed. During Weeks 5-7 vocalization was gradually restored in rats that previously received OP and partially inhibited in animals previously treated with TP. These results indicate that; (1) vocalization may not be dependent on the presence of testicular androgens and, (2) OP has a gradual inhibitory effect on vocalization when given at high doses and this effect is reversible.


Effect of amygdalectomy on habituation and CER in rats.

Amygdalectomized, Sham operates and unoperated rats received 20 habituation trials followed by CER training during which the habituation stimulus was made a CS for 10 CS-UCS pairings. Although no reliable differences in rate of magnitude of habituation as measured by suppression ratio magnitudes and ITI durations were apparent between any groups, these same measures indicated that substantial deficits in conditioned suppression were produced by bilateral amygdalectomy. In addition the lesion produced a reliable deficit in unconditioned suppression and a slight but reliable reduction in the number of ccs of water consumed in a 24 hour period. These results are more consistent with the hypothesis that amygdalectomy interferes with the arousal of fear than with the proposals that this lesion produces deficits in habituation or in response inhibition.


Copulatory behavior of golden hamsters: effects on pregnancy.

Two experiments were conducted to study the role of male copulatory behavior in initiating physiological responses necessary for pregnancy in female hamsters. In Experiment 1, it was found that copulation beyond the first ejaculatory series is critical to attainment of maximal probabilities of pregnancy. Whereas all females became pregnant when mated to a criterion of sexual satiety, only 20 percent were pregnant after one ejaculatory series. The relationship between increased copulatory stimulation and increased probability of pregnancy was further refined in Experiment 2. Females required more than 4 ejaculatory series to maximize the probability of pregnancy. Mounts without intromission had no effect. Neither parturition number of ova shed, nor little size appeared affected by amount of copulatory stimulation. A coadaptation between the copulatory pattern of the males and the response systems of the females of several rodent species appears to have evolved and to aid successful reproduction.


Locomotor and avoidance behavior in rats with partial or total hippocampal perforant paths sections.

Bilateral partial damage to the hippocampal perforant paths in rats produced impaired two-way active avoidance performance, while the behavior in open field, passive and one-way active avoidance remained unchanged. Total disruption of the perforant path projection resulted in increased open field activity and impaired one-way active avoidance, but normal passive avoidance behavior. The results are discussed in terms of reduced sensory information to the hippocampal formation.


Changes in alpha rhythm asymmetry during learning of verbal and visuospatial tasks.

Alpha activity in the two cortical hemispheres was examined during learning and overlearning of a verbal and a visuospatial task. Compared to a pretask baseline condition, the amount of alpha activity during the tasks was decreased. An increase in alpha activity was found from learning to overlearning in both tasks. A greater amount of alpha was found in the right hemisphere for both tasks. In addition, no difference in the degree of alpha asymmetry was found between the tasks. This was discussed in light of prior contrary findings. A significant positive correlation was found between change in learning rate and change in alpha asymmetry during the verbal task. An interpretation of this finding was offered in terms of the level of hemispheric activation reflecting the degree of task engagement.


Somatosensory evoked responses and slow potential oscillations in human scalp recordings.

Average evoked responses obtained from the frontal, parietal and vertex regions, by electrical stimulation of the median nerve or common peroneal nerve, indicate the presence of time locked components which occur as late as 500 to 3500 msec after the stimulus. Spectral analysis shows that these components are distributed mostly in the 1.5 to 2 and 3.6 to 4 Hz frequently bands, and their presence in the evoked response may be due to the driving, by the stimuli of oscillations of similar frequencies which can be seen in the spontaneous activity recorded from the same region.


Effect of the light-dark cycle on neuroendocrine and behavioral responses to scheduled feeding.

Rats, nocturnal animals, adapt both behaviorally and physiologically to a restricted feeding schedule. Such adaptations occur faster and more efficiently during the dark portion of a light-dark cycle as indicated by measurements of latency to eat, amount of food consumed, body weight, and insulin levels.


Resection  of the hook of the hamate. Its place in the treatment of median and ulnar nerve entrapment in the hand.

Poor results can be anticipated with conventional surgical decompression of nerves entrapped within the hand in (1) those with underlying systemic disease causing primary neuropathy, (2) those with combined median and ulnar nerve palsies, and (3) those who have been previously operated upon for nerve entrapment within the hand. Eighteen patients belonging in these categories were surgically treated by resection of the hook of the hamate and (in some) by intraneural neurolysis. Using this technique, we have decreased our failure rate from 20 percent to less than one percent. We believe that failures can be eliminated if the patients destined to have poor results from the usual treatment are identified preoperatively and a more aggressive surgical decompression is used on this "at risk" group.


Lymphedema. A clinical review and follow-up study.

In a retrospective study of primary lymphedema, we found that the age of onset ranged from 0 to 16 years; sex did not appear to be a factor; and treatment was preventive rather than surgical. Thirteen patients were available for follow-up studies, the time interval being at least 6 years. The degree of swelling at the time of the follow-up examination was defined as mild, moderate, or severe. In patients with mild and moderate swelling the edema was not progressive and surgical treatment was not indicated. Severe swelling appeared to be associated with congenital lymphedema and with repeated infection. Pressure-support treatment can be effective in the reduction of swelling or in the prevention of further swelling, if applied constantly over a long period of time. The authors discuss the histological similarity between lymphedema and lymphagioma, and present an anatomical classification for the two entities.


Results of various operations for sacrococcygeal pilonidal disease.

A comparative evaluation of 4 operations designed to treat sacrococcygeal pilonidal disease is presented, to show the duration of treatment time and the recurrence rate. Case records of 112 patients (131 operations) were studied. The results indicate that the healing times with the excision and Z-plasty operation are clearly less than those obtained by incision with drainage and packing, excision with primary closure, or excision and lay open. The overall recurrence rate in this series was 28 percent, all occurring within 3 years of the first operation. With the exception of the Z-plasty operation, other methods required considerable outpatient treatment time and were more susceptible to recurrence. We suggest that by reconstructing the intergluteal cleft, the likely effect of the Z-plasty operation is to eliminate factors that may promote pilonidal disease in this region.


Implications and applications of recent research on feminine development.

The traditional feminine role pattern is no longer adaptive and functional for many women, because of pressures for change associated with such components of the social climate as the lengthening life span and concern about the population explosion. It is no longer physically possible nor considered socially valuable to spend a lifetime bearing and rearing children, even for those women who desire to do so. Thus the prospect or actuality of defining one's life by the wife-and-mother role creates anxiety and anger, which is increased by the awareness that society pays only lip service to so-called "feminine" qualities and behaviors, reserving power and prestige for those who achieve high status in the world of work. Clearly women need alternate bases of gratification and identity. However, these involve interconnected changes that are often painful and that require understanding and support from others which has been slow in coming. The general purpose of this paper is to provide evidence that changes in the feminine role pattern are a matter of urgency and will be beneficial to both sexes.


Postwar writing and the literature of the women's liberation movement.

This article explores the relationship between both popular and scholarly writing about women in the postwar years 1946 to 1962, and the literature of the women's liberation movement written from 1963 to the early 1970s. The current feminist movement was particularly eager to discredit Freudian theories of female psychosexual maturation. This women's liberationist focus was entirely appropriate, since Freudian theories about women represented the last respectable academic prop upholding a dichotomous estimation of the socio-politico-economic potential of the sexes--i.e., sexism, as it has come to be called. Postwar scholarship had manifested a split perspective--that is, it was anti-Freudian and pro-feminist or pro-Freudian and anti-feminist. What is more, considerable academic writing about the "woman question" proposed an expanded role for females, advocating a point of view quite similar to that of contemporary feminists. In contrast, the popular literature--e.g., Life, Look, Ladies Home Journal, and the like--proposed only a Freudian (dichotomous) answer to the question, "What are the proper roles of the sexes?" While the findings with regard to popular writing are not too surprising, the extent of early scholarly support (i.e., prior to the women's liberation movement--roughly before 1963) for an expanded role for women was entirely anticipated.


Marriage and the development of schizophrenia.

The families of orientation of schizophrenic patients have already been the subject of much research. By shedding light on the nature of the disturbed interactions between parents and children, such research has added greatly to our understanding of the psychodynamics of schizophrenia. This research has also provided a basis for the development of the family therapy of schizophrenic patients. However, little attention has so far been given to the psychydynamic study of schizophrenic patients' own marital relationships. Yet the study of the mutual relationships of patients and their spouses--particularly in cases where the psychosis set in only after the patient was already married--might elucidate the problems associated with the onset of schizophrenia and, at the same time, be of significance for family therapy. The present paper, which reports a study of 30 married couples in which one spouse had fallen ill with schizophrenia during the marriage, had its origin in expectations of this kind.


The struggle in psychotherapy: its influence on some theories.

If the theories of Jerome Frank, Jay Halley, and Hans Strupp are considered as a conversation with the spirit of psychoanalysis, the subject of the conversation appears to be the struggle involved in psychotherapy. Beyond implying that there is such a struggle, the theories do not satisfactorily establish its nature. The author suggests that the struggle may have to do with the therapist's insistence on what Frank calls a sheltered environment for patient experimentation.


Conditioned aversion by amphetamine: rates of acquisition and loss of the attenuating effects of prior exposure.

Chronic prior treatment with amphetamine greatly attenuates the conditined aversion to saccharin that may be produced by amphetamine. Two experiments were designed to determine some of the limiting conditions of this phenomenon. In Experiment 1, chronic treatment with 7.5 mg/kg of amphetamine was administered for 0, 1, 5, or 20 days prior to pairing saccharin with an injection of 1.0 mg/kg of d-amphetamine sulphate. The results indicate that between 5 and 20 days of treatment were necessary for the treatment to be effective in attenuating conditioned aversion. In Experiment 2, rats were withdrawn from treatment with 20 mg/kg of amphetamine for 1, 7, or 14 days prior to conditioning trials with 1.0 mg/kg of amphetamine. The prior treatment lost it effectiveness in attenuating conditioned aversion between 7 and 14 days after withdrawal. Although alternative explanations are possible, the time intervals required for acquisition and loss of the effectiveness of prior treatment are consistent with the hypothesis that tolerance is the mechanism underlying the observed effects.


Cholinergic modulation of an opposed effect of d-amphetamine and methylphenidate on the rearing response.

Rats given d-amphetamine (1 mg/kg) engage in frequent, short-duration rearing responses, whereas rats given methylphenidate (1 mg/kg) make less frequent, long-duration responses. The effects on this behavior of mixing d-amphetamine or methylphenidate with scopolamine or physostigmine suggest that this opposed action on rearing response duration is related to cholinergic-catecholaminergic balance. The anticholinergic agent scopolamine produces changes in rearing response duration similar to those produced by d-amphetamine, while the cholinergic agent physostigmine lengthens response duration and further potentiates this effect of methylphenidate.


Colour preferences in the pigeon: a behavioural and psychopharmacological study.

Ten London pigeons were tested in an operant apparatus, and found to have marked colour preferences, blue being preferred over green, followed by yellow and red. The effects of 2 tranquilizers, diazepam and chlorpromazine, were studied and it was found that diazepam released responding, and chlorpromazine suppressed it. Diazepam also tended to abolish colour preference, whilst chlorpromazine was effective only at the highest dose used (5.00 mg/kg). The implications of these findings, particularly in relation to the design of experiments and to the aversiveness of certain stimuli, are discussed.


Effects and plasma levels of N-desmethyldiazepam after oral administration in normal volunteers.

In the course of a previous study on the pharmaco-kinetics and effects of diazepam in anxiety patients, it was hypothesized that the N-desmethyl derivative is a disturbing agent causing side effects. The present study served to test the validity of this assumption. Diazepam and N-desmethyl-diazepam, the latter as a separate drug, were orally administered to 6 subjects, each drug during 7 days, 15 mg daily in divided doses. Using a randomized, placebo controlled, double-blind design, subjective and observer ratings of a wide range of clinical effects were made. Plasma levels of the benzodiazepine compounds were determined by the G.L.C. method. Results showed that steady state plasma levels were reached on the 5th day; the N-desmethyldiazepam, considering its lower clearance rates, is a longer acting drug than diazepam; that both substances induce hypnosedative effects, mood changes, and somatic disturbances and facilitate sexual behaviour in normals; that desmethyldiazepam is a more effective hypnosedative and mood-lowering substance as compared to equal doses of diazepam. Further comparisons in anxiety patients are recommended in order to find out if the specific desmethyldiazepma effects are therapeutically favourable or disturbing.


Probenecid: dosage, levels in plasma and cerebrospinal fluid (CSF) and influence upon CSF levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the rabbit.

Probenecid retards the efflux of acid monoamine metabolites from the brain tissue and CSF to the blood. The probenecid-induced accumulation of these metabolites is held to be indicative of the turnover rate of the corresponding amines. Although the penetration of probenecid into the CSF does not proceed at a constant rate, Korf et al. (1972) and Sjöstrom (1972) have shown a correlation between CSF levels of probenecid and that of HVA and 5-HIAA. In this study an attempt was made to establish the relationship between doses of probenecid and levels of this compound in plasma and CSF; between levels in plasma and CSF; and between CSF levels of probenecid and of HVA and 5-HIAA. This study was performed in a homogeneous group of laboratory rabbits. All correlations proved to be significant. The implications of these results for studies using the probenecid technique are discussed.


Behaviorally induced sensitivity to the discriminable properties of LSD.

Rats were initially trained to discriminate LSD from saline in two-lever operant chambers by reinforcing responses only on one lever following intraperitoneal injections of 80 mug/kg of LSD and only on the other lever following saline injections. Choice responding during extinction periods (no water reinforcement for either response) indicated a high level of discriminability (95% correct) following either LSD or saline. A dose-response curve for LSD, obtained by tests for lever choice after injections of 10, 20, 30, 40, 50, and 60 mug/kg, indicated that 10 mug/kg produced only 30% responding on the LSD lever. This percentage was increased (to 83%) by reinforcing responding on the LSD lever following injections of 10 mug/kg. Subsequent tests indicated that doses of 5.0 and 2.5 mug/kg produced a majority of responses on the LSD lever. Since at these low doses LSD has few measurable biochemical or behavioral effects, we hypothesized that the discriminable cue of LSD is related to direct stimulation of central serotonergic receptors.


Influence of delta9-tetrahydrocannabinol on partial reinforcement effects.

Two experiments were performed with rats trained with either continuous reinforcement (food) or random 50% partial reinforcement for running in a straight alley. Half the rat were trained with daily injections of 0.5 mg/kg delta9-tetrahydrocannabinol (THC) and half with vehicle injections, all animals being extinguished with vehicle injections in Expt. 1 and with THC injections in Expt. 2. The partial reinforcement acquistion effect was abolished by THC during training; the partial reinforcement extinction effect was abolished by THC either during training of during extinction. In these respects THC resembles amylobarbitone and alcohol.


The effects of serotonin on feeding in the rabbit.

Serotonin infused through hepatic-portal cannulae of rabbits decreased food intake in a free-feeding condition. Following a 12 hr food deprivation period similar doses of serotonin increased food intake. Other investigators have shown release of serotonin to food and related stimuli. Our results demonstrate that serotonin is not a simple "satiety hormone" but suggest that it may be importantly involved in short-term regulatory mechanisms of feeding.


A relationship between hexobarbitone sleeping time and susceptibility to mescaline in mice from different strains.

Males from the following strains were surveyed with respect to their hexobarbitone sleeping time: A2G, C57BR, C3H, F/st, CBA, ICFW and Schneider. Males from the same strains had previously been surveyed with respect to the inhibitory effect of mescaline on their emotional defaecation. There is a strong interstrain correlation between the 2 measures. This correlation was unexpected on theoretical grounds and may have important pharmacogenetic implications.


Effects of prior experience on differential learning under amphetamine.

Differential learning of operant behavior under non-drug and amphetamine states was explained with a "drug-behavior-reinforcement interaction" process. When a drug affects the relationship between ongoing behavior and existing reinforcement contingencies, the sets of behavioral patterns subjected to the process of reinforcement or non-reinforcement under a drug may differ from the patterns under non-drug conditions. If, following sufficient training, the drug conditions are then changed, persistence of these behavioral patterns may result in a difference from those patterns produced if acquisition occurs solely under non-drug conditions. To investigate this process, groups of rats were given varying amounts of non-drug acquisition training on a response-duration differentiation task before being given extended training under 0.75 mg/kg d-amphetamine. All groups were then tested under non-drug conditions. Amphetamine significantly enhanced performance, and this enhancement transferred to subsequent non-drug conditions. However, if non-drug training occurred before drug training, this enhancement was greatly attenuated. Furthermore, only those behavioral components under which amphetamine led to an increase in reinforcement rate showed enhancement in the non-drug state. The results, which supported the present position, were discussed in relation to a "stimulus generalization decrement" explanation of differential learning under amphetamine.


[Rationalized lithium adjustment by load-test (author's transl)].

The lithium blood level 24 hrs after a priming dose of lithium is a prognosticator for the therapeutic dosage required. Exactly 24 hrs following the intake of 24 mval lithium (lithium carbonate, retard form) venous blood serum is analyzed for lithium content. The necessary therapeutic dose can be inferred from a regression line which shows the negative interrelation between the 24 hr value and the therapeutic quantity of lithium necessary to achieve a blood level of 0.9 mval/1 under steady state conditions. Low 24 hr levels require high maintenance doses and vice versa. This procedure shortens the time of dose adjustment and avoids undesirable side-effects in the beginning of treatment which otherwise are not seldom the cause for the cessation of lithium intake.


Modification of the behavioral response to drugs in rats exposed prenatally to chlorpromazine.

Female rats exposed prenatally to low levels of chlorpromazine were less susceptible as adults to the rate-reducing effects of chlorpromazine and pentobarbital on fixed-interval performance of a food-reinforced operant. Males were not significantly affected by prenatal treatment.


Chlorpromazine effects on brain activity (contingent negative variation) and reaction time in normal women.

Electrical brain activity (contingent negative variation of CNV) and psychomotor behavior (reaction time or RT) were measured after 50 mg of chlorpromazine (CPZ) or placebo were given orally to 28 normal women. CPZ reduced CNV 2 and 3 hrs post-drug and slowed RT 3 hrs post-drug. CNV amplitude appears to be an accurate indicator of drug-produced changes in alertness.


[Volumetric follow-up measurements in normal and pathologic lymph nodes (author's transl)].

Alteration of Lymph node volume are measured in different groups of patients. Irradiated Lymph nodes diminish volume significantly more and faster than non-irradiated ones. Lymph nodes with reactive hyperplasia with/without irradiation show a significantly smaller volume decrease than normal Lymph nodes. Malignant systemic diseases have a significant higher volume decrease than normal or reactive hyperplastic Lymph nodes with identical irradiation-dose.


Criteria-referenced approach to clinical practicum.

A great deal of interest has been generated recently in improving clinical instruction and evaluating performance. A criteria referenced approach was described in general terms in RADIOLOGIC TECHNOLOGY 46: 275-278, 1975. This paper provides specific rather than general information. Specific objectives are written to identify learning expectations during clinical practice in a 24-month radiologic technology program. The conditions under which the student will demonstrate his mastery of the objectives and the criterial for an acceptable performance level for each objectives are not included in this paper.


[Cinegeometric analysis of left ventricular function in normals and in patients with isolated stenosis of the ramus anterior descendens (author's transl)].

The left ventricular function was evaluated by a cineangiographic method. 28 normals and 36 patients with an isolated stenosis of the anterior descending branch of the left coronary artery underwent this procedure. From single plane RAO-LV-cineangiograms following parameters were calculated: LV-volumens (EDV, ESV) according to the area-length method, ejection fraction (EF), percentage shortening of the medial perpendicular short axis (delta M, delta MPL), mean velocity of circumferential fiber shortening (VCF, VCFPL). Patients with comparable ramus anterior descendens branch findings can have normal- or abnormal pattern of LV-contraction. The critical cineangiographic parameters of left ventricular function are significantly decreased at rest in ramus anterior descendens lesions with normal systolic anterior wall motion in comparison to the normal collective. Hypokinesis, Akinesis and aneurysms deteriorate parameters of LV-function.


Howard University program for radiotherapeutic technology.

The Howard University program for radiotherapeutic technology provides for a career ladder with steps of two years. After the first two years everyone must take and pass examination in radiotherapeutic technology given by The American Registry of Radiologic Technologists. The candidate then can proceed with two years of university courses to a Bachelor of Science degree. Depending upon his interest, he can emphasize business, education, or science. The latter would qualify him for application medical school. The core of the curriculum for the first two years consists of clinical work in the radiotherapy department every morning and of two integrated multidisciplinary courses in the afternoon, namely, life sciences (anatomy, physiology, pathology and oncology) and natural sciences (mathematics, physics, radiation physics and treatment planning).


[Angiography and jaundice (author's transl)].

Results of celiacography and mesentericography in 198 patients with jaundice are reported. The angiographic findings in 66% were consistent with malignant tumors. In this series angiography confirmed the diagnosis of obstructive jaundice in 83%. The value of angiography is emphasized to decide whether a tumor can be resected.


Counseling in radiologic technology programs.

Rarely do radiologic technology programs have adequate faculty to provide full-time counselors for the student's personal, professional, and academic problems. The problems of using educational or administrative personnel as part-time couselors are discussed and the utilization of interested staff technologists in the role of student counselor is recommended.


A look at radiologic technology education.

Radiologic technology education has been progressing for the last 80 years; however, we have seemingly reached a plateau. Educators in the profession believe there is need for a change in direction due to demands of the manpower market and outside agencies. The direction radiologic technology educators should follow has been questioned, but no definite answer has resulted. With these thoughts in mind, a decision was made at the Duke University Medical Center to survey the nation and collect data to aid its particular problem, as well as to lend educational direction.


Rebuttal to TV show: "coffee, tea or radiation".

On 22 October 1974, CBS News presented a segment "Coffee, Tea or Radiation" on its program "Magazine". The program focused on the hazards of transporting radioactive materials by common carrier, especially by air. The presentation provoked strong reaction among some knowlegeable individuals. The text o this article is a letter sent by the author to Perry Wolf, CBS News, New York. A copy was  made available to the American Society of Non destructive Testing through Walter P. Peeples, Jr., president, Nuclear Environmental Engineering, Inc., Houston, Texas.


Polyps caused by gastric erosions.

Gastric erosions, a disease with a tendency to recur through decades, may in advanced age and anacidity give rise to polyps. These histologically benign polyps may be recognized by clinical methods of examination.


[Multilocular tumors of small intestine (author's transl)].

Tumors of small intestine can be recognized in time and evaluated histologically by means of roentgenographic and endoscopical-bioptic methods, respectively. Among radiologic techniques, the double contrast examination of the small intestine has especially high diagnostic value. On the other hand, selective angiography reveals bleeding of accompanying small intestinal tumors. Out of 23 patients with these tumors -- diagnosed in the Medical Department of the Erlangen University from 1968 to July 1974 -- there was one case with multilocular occurrence; the diagnostic efficiency of double contrast technique proved to be particularly suitable in this patient.


[Intramural gas collection in the small bowel (author's transl)].

Intramural gas collection in a bowel segment is an important roentgenological sign, consistent with necrosis of the bowel wall. This is demonstrated by an example of jejunal volvulus and an inflammatory conglomeration of intestine. The diagnostic interpretation must be completed by the clinical picture and other signs of intestinal ischemia.


[A new contrast medium (author's transl)].

Report about a new roentgen contrast medium which contains as salt-forming cations the physiologic alpha-amino acids L-lysine, L-ornithine instead of the body-foreign N-methyl-glucamine base and as anion diatrizoate acids. Favourable results concerning clinical and roentgenological aspects of the lysine salt of diatrizoate acid are derived: general and local tolerance in angiographic and urologic examinations are good, pulse rate remains stable, blood pressure fluctuations are minimal.


A simple method for routine double-contrast study of the upper gastrointestinal tract.

A technique for routine double-contrast study of the stomach and duodenum is presented. It requires neither nasogastric intubation nor hypnotic drugs. The authors emphasize the technical factors and maneuvers which result in optimal mucosal coating and unobscured double-contrast views of the stomach and duodenum. The radiological error rate was 7% in 190 patients; a marked improvement over results produced by the standard barium study. In a consecutive series of 1,000 patients superficial gastric erosions were demonstrated in 19 patients. It is recommended that such a technique be applied to the routine radiological study of the upper gastrointestinal tract.


Demonstration of erosive gastritis by the double-contrast technique.

The value of the routine pharmacologically-aided double-contrast examination of the upper gastrointestinal tract in demonstrating superficial gastric erosions was assessed. Ten cases of erosive gastritis were diagnosed during a six-month period. It appears that erosive gastritis is more common than generally believed. Diagnosis requires relaxation of the stomach and demonstration of fine mucosal relief by the double-contrast technique.


The stalactite phenomenon in double contrast studies of the stomach.

Supine vertical beam films in double contrast studies of the stomach often show "barium spots" projecting on anterior wall polyps and folds. The supposition that these spots are caused by droplets of barium hanging from such protuberances is proved radiographically using horizontal beam techniques.


Plain film diagnosis of retrocecal appendicitis.

The plain radiographic findings encountered in 21 patients with acute retrocecal appendicitis were analyzed. In descending order of frequency, the following changes were noted: (a) edema infiltration of properitoneal fat; (b) mass between properitoneal fat and ascending colon; (c) a coprolith above the anterior superior iliac spine; (d) gas in the appendix; (e) haustral irregularity of the ascending colon; and (f) retrocecal extraperitoneal gas.


Uterine artery calcification: its association with diabetes.

Uterine artery calcification was observed in 26 patients. Fourteen of the 22 with adequate cliniccal information had diabetes mellitus. This is considered a significant association by the authors and calcification should raise the question of diabetes.


Uriniferous perirenal pseudocyst: new observations.

The chronic encapsulated extravasation of urine, most accurately designated as uriniferous perirenal pseudocyst, causes urine to collect within a characteristic complex of radiographic findings including an elliptical soft-tissue mass in the cone of renal fascia. This results in the flank oriented inferomedially with upward and lateral displacement of the lower renal pole, medial displacement of the ureter, obstructive hydronephrosis, and perhaps evidence of extravasation into the mass. Since the clinical recognition of the mass is typically delayed several weeks following the original traumatic episode, prompt radiological diagnosis is essential before irreparable damage to the kidney occurs.


Tibiotalar slant: a new observation in sickle cell anemia.

Several examples of a peculiar deforming process about the ankle joint resulting in a tibiotalar deformity are reported. When found in black patients, further examination for sickle cell disease should be done. No previous mention of this deformity in connection with sickle cell anemia has been found.


Pulmonary parenchymal Hodgkin's disease. RPC from the AFIP.

The radiographic findings of mediastinal lymphadenopathy associated with pulmonary parenchymal nodules (with possible cavitation) should alert the radiologist to the possibility of Hodgkin's disease. The pulmonary parenchymal lesions are almost always associated with lymphadenopathy and are rarely an isolated finding.


Theory of image reconstruction in computed tomography.

Mathematical methods are of central importance in the new technologies of radiographic and radioisotopic image reconstruction. The most important procedures are classified as Back-projection, iterative, and analytical (Two-dimensional Fourier, Filtered Back-projection). Back-projection played an important historical role but is no longer used because of sizable artifacts. Analytical methods excel in speed and accuracy when a large number of projections are available and are extensively used in x-ray imaging. Iterative reconstruction is more attractive when the number of views is limited, if noise is significant, and if additional factors, e.g., gamma-ray attenuation, are present. For these reasons, iterative methods are widely used in radioisotope imaging.


Correlation of effective atomic number and electron density with attenuation coefficients measured with polychromatic x rays.

Attenuation coefficients of nine different plastics and water were measured with EMI computed transaxial tomography (CT) and radioisotopic sources with photons of 14 to 136 keV. The EMI values were correlated with physical density, electron density, and atomic number cubed (Z3). The best correlation was obtained with electron density, the exception being the value for water. This descrepancy was explained on the basis of X-dependent photoelectric absorption with verification from monoenergetic measurements.


An extravascular component of contrast enhancement in cranial computed tomography. Part I. The tissue-blood ratio of contrast enhancement.

One can calculate the tissue-blood ratio of enhancement by analyzing the quantitative aspects of the CT scans of the cranium and blood samples both before and after the injection of contrast medium. This ratio is equivalent to that between the iodine content of a given volume of tissue and an equal volume of blood. Analysis of 47 normal patients, including 27 with pathological brain lesions, indicated that there is significant extravasation of contrast medium in patients with such lesions.


An extravascular component of contrast enhancement in cranial computed tomography. Part II. Contrast enhancement and the blood-tissue barrier.

The authors provide evidence of significant extravasation of contrast media responsible for the contrast enhancement of pathological tissue on computed tomography. The tissue-blood ratio of enhancement was calculated by the EMI scanner in 2 patients after injection of contrast material and prior to surgery; tumor-blood ratios for red blood cell and plasma tracers were calculated after surgery. The ratios of enhancement demonstrated the analogy between contrast enhancement and the leaking of radionuclide across the blood-brain barrier. This phenomenon may cause error if this technique is used for the measurement of cerebral blood volume. The area for complementary roles of CT and radionuclide brain imaging seems to be narrower than expected.


Recent ischemic brain infarcts at computed tomography: appearances pre- and postcontrast infusion.

Thirty-seven cranial computed tomography (CCT) scans of proved or highly probable recent ischemic brain infarcts were analyzed visually and numerically, with results organized by infarct age. The lesions typically appeared as homogeneous low density abnormalities, with no significant difference in scan characteristics between infarct age groups, i.e., it was not possible to determine the age of an infarct by its noninfused, CCT appearance alone. Eight infarcts showed "mass effect," and 4 of the 20 contrast-infused cases demonstrated marked density augmentation of "blush," indicating that infarcts may resemble tumor in both of these properties.


Computed tomography in diastematomyelia.

The diagnosis of diastematomyelia was confirmed in 2 patients by computed tomography (CT). Abnormalities of the vertebral bodies, pedicles, lamina, and spinous processes were defined and the diastematomyelic spurs were visualized.


The use of computed tomography for radiation therapy treatment planning.

In this treatment planning method, information from total body scans is fed into a radiation therapy treatment computer, the Artronix PC-12 system with 16K core. By providing an accurate profile of the patients's anatomy, total body computed tomography may contribute greatly to the solution of complex treatment problems involving the head and neck, thorax and abdomen.


Potential artifacts associated with the scanning pattern of the EMI scanner.

Physical and geometrical considerations of the EMI scanner are used to predict that regions of the head can be missed by adopting a scanner procedure based on the nominal EMI slice thickness. Using a nominal slice thickness of 1.3 cm and effective focal spot length of 12 mm, one can predict that in the central portion of the head, up to 8% of the region scanned may not be imaged. Moreover, it is shown that simultaneous monitoring of a single focal spot by two adjacent detectors, as in the EMI system, would lead to significant overlap between the two adjacent EMI slices resulting in dual imaging. Experimental examples are shown to illustrate these two artifacts in the EMI scanner.


Cerebral circulation after cardiac arrest. Angiographic and carbon black perfusion studies.

Cardiac arrest of 2-15 minutes was induced in 14 dogs. When circulatory arrest lasted longer than 5 minutes, abnormal cerebral angiographic findings were seen 3-4 hours after resuscitation, consisting of (a) marked prolongation of the arterial phase in both intracranial and extracranial arteries, and (b) faint (poor) visualization of the venous phase. No significant abnormalities were noted in dogs arrested less than 5 minutes, or in the control group. Carbon black perfusion studies showed multiple focal areas of small patchy and diffuse coarse reperfusion defects at the arteriolar-capillary levels in dogs arrested longer than 5 minutes. A combination of vascular and parenchymal changes during ischemia may be the cause of these findings.


133Xe muscle clearance: a screening test for arterial occlusive disease.

133Xe muscle clearance following ischemic exercise provides a simple, well-tolerated screening procedure for evaluating patients suspected of having arterial occlusive disease in the lower extremeties and may be useful in the follow-up of patients who have undergone corrective arterial surgery. It can be performed in nuclear medicine units capable of doing renography, and the authors feel it should be used prior to undertaking more invasive procedures such as arteriography. Methods and results of tests involding 92 legs in men are described.


Liver scan "hot spot" in hepatic veno-occlusive disease.

A focal "hot spot" seen on liver scan in an unusual case of hepatic veno-occlusive disease bore striking similarities to scanning patterns in superior vena cava syndrome. The findings are also compared to those reported in Budd-Chiari syndrome.


67Ga radionuclide imaging in Burkitt's lymphoma.

Whole-body gallium imaging was evaluated as a diagnostic tool for 14 patients with Burkitt's lymphoma, and a dramatic gallium affinity for the tumor was demonstrated. The gallium image is recommended as a staging procedure and as an effective test for determining the therapeutic response.


Are all gallium citrate preparations the same?

Recent studies on brain imaging using 67Ga citrate from three different manufacturers revealed some clinical differences. Using chromatographic techniques, it was found that 67Ga citrate supplied by vendor A clearly differed from those of vendors B and C in mobility. When citrate was added to material of vendor B to bring the final concentration to 25 mg/ml, the chromatographic mobility increased dramatically. Addition of benzyl alcohol had no effect. The mechanisms involved in causing these chromatographic changes are not clear; however, the in vitro variations noted indicate a difference in chemistry which may ultimately affect the distribution and localization of the radiopharmaceutical.


Staphylococcal osteomyelitis, sepsis, and pulmonary disease. Observations of 10 patients with combined osseous and pulmonary infections.

The clinical and roentgenographic findings in 10 patients with combined staphylococcal infection fo the bones, joints, and lungs are reviewed. Chest roentgenograms early in the course of the illness suggested septic embolic disease, but in most cases the associated osseous infections were overlooked. Primary therapy, directed toward the sepsis and pulmonary complications, was often unsuccessful until the associated osteomyelitis was recognized and treated. The radiologist and clinician should recognize the roentgen pattern of septic pulmonary emboli and be alert to the possibility of associated skeletal infection. Surgical drainage is often necessary.


Radiographic findings in previously untreated children with non-Hodgkin's lymphoma.

The initial radiographs of 51 consecutive, previously untreated children with non-Hodgkin's lymphoma were reviewed. The chest radiograph was abnormal in 37%, with pleural effusions seen in 14% of patients. Lymphography, readily performed in children, was positive in 30% of the successful studies. There was a high incidence of bone lesions (18% of patients), due in large part to involvement of the facial bones; all were symptomatic and/or seen on the routine chest and abdominal radiographs. Intrinsic disease of the small bowel (10%) and colon (8%) was also associated with symptoms, so that the value of routine barium studies in asymptomatic children is questioned.


Gray scale ultrasonic angiography of the upper abdomen.

Because of the limited resolution of conventional ultrasonic B-scanning units, visualization of normal vascular anatomy in the upper abdomen has been largely restricted to the aorta. By utilizing the newer "gray scale" equipment, it is now routinely possible to demonstrate the inferior vena cava and portal veins as well as several smaller epigastric arterial and venous branches with considerably improved clarity. This report presents the normal ultrasonic vascular anatomy of this complex area detected thus far and some preliminary observations regarding pathological alterations. Future potential applications of these findings are also discussed.


Ultrasonic diagnosis of omental cysts.

The ultrasonic findings in 2 patients with omental cysts are described. The correct diagnosis was made by combining ultrasound observations with gastrointestinal contrast study results, plain film findings, medical history and physical examination. Ultrasonically, an omental cyst appears as a well-outlined, sonolucent, transonic abdominal mass. Ultrasonography is recommended as an aid in the preoperative diagnosis of mesenteric cysts.


Postirradiation atrophic changes of bone and related complications.

The sequence of radiographically visible changes about the shoulder girdle following irradiation was analyzed in 49 patients who received 200 kV irradiation, in 50 who received 25 MeV betatron photon irradiation, and in 20 who received cobalt-60 irradiation. The changes were dose related and were most evident in the kilovoltage group, but also occurred following megavoltage therapy. Atrophic changes may be complicated by fracture, true necrosis, true osteitis or sarcoma. These atrophic changes have clinical significance similar to the atrophic changes that occur in skin and mucous membranes. The terms radionecrosis and radiation osteitis as applied to these changes should be abandoned since they imply a more serious process than is actually present. Biopsy should be avoided if possible since trauma and secondary infection could lead to true necrosis.


The role of radiotherapy in renal involvement in acute childhood leukemia.

Twenty-one children with acute leukemia received irradiation to the renal area for the following reasons: hypertension (2 patients); oliguria (5 patients); mass-related symptoms (5 patients); and as an adjuvant to supportive medical management in preventing renal failure (9 patients). All but 2 patients exhibited bone marrow exacerbation. The results of treatment with radiotherapy are discussed. Total doses in the range of 600-1,200 rads are suggested.


Patient exposures from film and xeroradiographic mammographic techniques.

Radiation exposures of several mammographic imaging systems, including (a) industrial film, xeroradiographic plates, the Du Pont Lo-Dose vacuum-cassette screen-film combination exposed with a molybdenum target tube and (b) xeroradiographic plates exposed with a tungsten target, were investigated with a thin-window ionization chamber and a range of exposures for different breast sizes was determined for each technique. The Lo-Dose system was found to provide high-quality diagnostic images with minimal patient exposure.


X-ray imaging with a scanning beam.

An x-ray imaging system that makes use of a rapidly scanning pencil beam of x rays to acquire images of any part of the body has been developed. The system is capable of generating and displaying images in 15 seconds, using extremely low radiation exposures. The principle of its operation, its unique imaging properties, and its possible applications are discussed.


Preliminary evaluation of di-iodo-triglucosyl benzene. An approach to the design of nonionic water-soluble radiographic contrast media.

A new compound, di-iodo-triglucosyl benzene (DTB), was synthesized and tested for contrast medium potential. It is stable and soluble in water, with a molecular weight of 864 and a viscosity of 33.3 cps at 40degrees C for a 66.6% w/v solution. It is rapidly excreted unchanged by the kidneys. Its estimated LD50 in mice at an intravenous injection rate of 330 mg l/min is 34.0 g/kg. It is highly hydrophilic and not epileptogenic, but its low iodine content (29.4%) makes it unfavorable for clinical use.


Myocardial mapping techniques and the evaluation of new 113mIn-labeled polymethylenephosphonates for imaging myocardial infarct.

The localization of 113mIn-ethylenediamine tetraethylenephosphonate and 113mIn-diethylenetriamine pentamethylenephosphonate in myocardial infarct induced in rabbits by coronary artery ligation was investigated. Double labeling of the same tissue with 45Ca ion was used as an index of tissue degeneration. The radioactivity ratio (40-50:1) of infarcted to normal myocardium was obtained 1.5 hours after injection and 2.5 hours after infarct. For the 45Ca-labeled phosphonate derivatives, a ratio of 7-6:1 was obtained at the same time. These agents will thus be useful for the detection and localization of acute infarct.


113mIn-labeled bone scanning agents.

Phosphonate analogs of EDTA and DTPA, in which the acetic acid has been replaced by methylene phosphonic acid (DTPMP and EDTMP) have been labeled with 113mIn and evaluated as skeletal imaging agents. Organ distribution in rats, blood clearances in dogs, and images obtained in rabbits are presented. 113mIn-DTPMP exhibits the desired characteristics to supplant 85Sr and other bone-seeking radiopharmaceuticals used in areas of the world where 99mTc is not routinely or regularly available.


Simplified interstitial therapy technique ("Vicryl" 125I) for unresectable lung cancer.

A simple technique of permanent radioactive implantation, originally developed for the increasing number of unresectable lung tumors, utilizes absorbable polyglactin sutures ("Vicryl") containing low intensity, long half-life 125I seeds.


A device to aid in positioning for the Andrén-von Rosen hip view.

The authors describe a device which simplifies positioning of the infant when using the Andrén-von Rosen hip view. This device facilitates achievement of the precise angles of abduction and rotation and aids in the diagnosis of congenital hip dislocation.


Use of the erect position for aspiration needle biopsy of diaphragm-based pulmonary lesions.

Lesions in the lower lung field may be obscured by an ascending hemidiaphragm when the patient is supine or prone. Use of the erect position for fluoroscopy facilitates percutaneous aspiration needle biopsy in such cases.


A copper partial-transmission block for use in whole-abdominal radiation therapy for ovarian carcinoma.

A copper partial-transmission block has been devised for use in abdomino-pelvic irradiation, permitting treatment of the pelvis at the conventional dose rate for therapy of the pelvis alone while treating the abdomen at a readily tolerated dose rate.


The air-contrast stomach examination: an overview.

An overview of current air-contrast stomach examination techniques is offered: (a) Hampton's technique which does not use distension; (b) the Japanese method which utilizes the relaxant drug Buscopan, good distension, and much patient rotation; (c) a third method in which no drugs are used but more distension is obtained than in Hampton's technique; and (d) the Australian mode which features relaxant drugs, extra dense barium, and little patient rotation. Experimentation with various techniques using newwer materials recently available should result in earlier diagnosis and better patient care in carcinoma and other stomach diseases.


Phosphoprotein formation and ADP-ATP exchange of cardiac sarcoplasmic reticulum.

Membranes of cardiac sarcoplasmic reticulum (SR) incorporate the terminal phosphate of gamma-[32P]ATP in the presence of Ca2+ and Mg2+ (0.85-1.3 nmoles/mg of protein). In the absence of Ca2+, or in the absence of Ca2+ and Mg2+, a value of about 0.3 nmoles/mg of protein was obtained. The Ca2+-dependent membrane phosphorylation is inhibited by ADP, NEM, and salyrgan, but not affected by dinitrophenol (DNP), azide, or ouabain. [32P]Phosphoprotein formed in the presence of Ca2+ is rapidly dephosphorylated by EGTA and/or ADP. The cardiac SR catalyzes a Ca2+-dependent [32P]ADP-ATP exchange and [32P]ATP formed = about 0.3 mumol/mg of protein X min at 25 degrees C, which is inhibited by NEM and salyrgan, but unaffected by DNAP, azide or ouabain. The demonstrated ADP-ATP exchange and the phosphorylated intermediate of the Ca2+-dependent ATPase would agree with a Ca2+ translocation mediated by the ATPase molecule, as proposed for skeletal sarcoplasmic reticulum.


Cytochemical studies on sarcoplasmic reticulum of heart and skeletal muscle.

Ultrastructural aspects and cytochemical localization of Ca uptake and of -SH groups involved in the calcium transport of vesicular fragments of sarcoplasmic reticulum (SR) from rabbit skeletal muscle and from dog myocardium were studied by positive and various negatively-staining techniques. Size, shape, and membrane structure as well as proportion of calcium-containing vesicles vary a great deal depending on the method applied. On negatively stained material sarcoplasmic reticulum derivatives are identifiable in both skeletal muscle as well as in heart preparations by the presence on the surface of the vesicular membrane of 40-A particles and the capability of accumulating calcium. The amount of these vesicles is lower in cardiac SR than in the skeletal SR; however, no qualitative differences can be observed. Vesicles of cardiac SR labeled with the electron dense -SH group reagent, Hg-phenyl azoferritin, also bind asymmetrically the marker only at the outer surface of the membrane-like microsomes of skeletal muscle.


Role of free calcium and ATP in calcium release from cardiac sarcoplasmic reticulum fragments.

Using both isotopic and spectrophotometric techniques to monitor the overall Ca++ binding and release reactions, we have studied the effects of the relative free concentrations of Ca++, sarcoplasmic reticulum fragments (SRF) protein, and ATP on spontaneous Ca++ release by SRF isolated from normal canine hearts. Low free [Ca++] was achieved by using a Ca-EGTA buffer; higher (micromolar) values were obtained by direct Ca++ additions throughout the reactions. ATP concentrations were stabilized by an ATP-regenerating system or an ATP trap. Concentrations of nucleotides in the reaction mixtures were also determined. Release depended in part on the [Ca++]/[ATP] and on the [ATP]. Spontaneous Ca++ release was prevented or slowed when the [ATP] was rapidly lowered with the ATP trap. ATP regeneration delayed, but did not prevent Ca++ release. Ca++-induced Ca++ release was found in the presence of ADP and ATP. Verapamil and D 600 did not affect release. The results may provide a basis for the slowed Ca++ release in SRF from failing hearts.


The role of mitochondria in the contraction-relaxation cycle and other Ca2+-dependent activities of heart cells.

The problem of whether mitochondria participate in the contraction and relaxation of heart by binding Ca2+ reversibly has been discussed actively in recent times. The role of mitochondria has not yet been conclusively established, but is suggested by several lines of evidence, particularly in amphibian hearts. Apart from contraction and relaxation, the Ca2+ transport system of mitochondria may influence many Ca2+-sensitive cell reactions. Some are mitochondrial (succinate oxidase, alpha-glycerophosphate dehydrogenase, pyruvate dehydrogenase phosphate phosphatase) and may control the operations of the respiratory chain and of the trichloroacetic acid cycle. Among the extramitochondrial Ca2+-sensitive reactions are phosphorylase b kinase, phospholipases, and pyruvate kinase. The latter activity has been studied in detail, and it has indeed been found that it can be modulated by mitochondria. It appears possible that the mitochondrial system for binding and transporting Ca2+ is an efficient means to regulate various phases of cell metabolism.


Calcium uptake and storage in isolated heart mitochondria influenced by sodium and potassium ions.

With rising concentrations of KCl the rate of Ca2+ uptake was moderately increased by 37 percent. NaCl induced a strong decrease of the rate of Ca2+ uptake from 498 to 194 nmoles of Ca2+ per sec-gm of protein (0-100 mM NAaCl). Elevating the K+/Na+ quotient from 0.1 to 15.7, we found a concomitant alteration of the rate of Ca2+ uptake which is mediated exclusively by sodium ions. These data indicate that with lowering of the K+/Na+ gradient there is a marked diminution of the mitochondrial rate of Ca2+ uptake and Ca storage. Our findings may contribute to answering how Na+-K+ exchange at the cell membrane may influence intracellular Ca2+ binding and Ca2+ turnover.


Functional differentiation of the transmembrane sodium and calcium channels in mammalian cardiac fibers by use of specific inhibitors.

During excitation of the mammalian ventricular myocardium two transmembrane inward currents occur: a fast Na current and a slow current carried mainly by Ca. The Ca current is strongly reduced by some organic compounds like verapamil and compound D 600 which are known to be very effective inhibitors of excitation contraction coupling. A similar decrease in the Ca conductivity of the membrane is produced by the bivalent cations, Ni, Co, and Mn. The blocking action of these organic and inorganic inhibitors is reversed by increasing the extracellular Ca concentration. The slow inward current can also be restored by Sr and Ba ions. The reduction of the slow Ca current produced by verapamil, D 600, Ni, Co, or Mn occurs selectively since the fast Na current remains practically unchanged. This demonstrates the existence of two separate membrane channels for Na and Ca which can be blocked independently. Thus it is possible to modify the contractility of the myocardial cell via the magnitude of the Ca current without disturbance of the transmembrane Na current which is intimately connected with excitability.


Myocardial function and subcellular calcium metabolism in chronic potassium deficiency.

Myocardial contractility was examined in whole, perfused hearts and in right ventricle papillary muscles of chronic K-depleted cats. Mitochondrial and sarcoplasmic reticulum (SR) calcium binding and concentration were estimated in the perfused hearts after exposure to 45Ca. In vitro SR Ca uptake was measured by the Millipore technique. Myocardial contractility was depressed in chronic potassium depletion and the degree of depression was related to the reduced SR Ca binding. These experiments suggest altered subcellular Ca metabolism as being a mechanism of depressed myocardial contractility in chronic K depletion.


Calcium movements controlling mammalian myocardial contractility: analog computation of contractile behavior assuming a multicompartmented model.

We present a model to be displayed on a medium scale analog computer, which describes excitation-contraction (E-C) coupling of the mammalian myocardium in terms of calcium movements occurring, on a sarcomere level, in a multicompartment system, Despite the fact that its mathematical formulations are oversimplifications of the mechanism involved, because the number of differential equations had to be limited, the model predicts with fair accuracy a large variety of inotropic phenomena thought to be the result of factors influencing cardiac E-C coupling in one way or another. Therefore, in its basic assumption, the overall concept might be correct, and if so, it should be possible to use the model in order to make predictions which can be tested experimentally and can help in understanding results which are otherwise difficult to interpret.


The site of healing over after a local injury in the heart.

The fluorochrome, Procion yellow, does not detectably penetrate the intact carciac cells of a living rat auricle, but stains the injured ifbers. When healing over is prevented in a calcium-free solution, the dye that penetrates through a point injury diffuses away from the damaged spot across the intercalated discs over a distance of several cell lengths. However, after an injury of the same size performed in a calcium-containing solution, Procion yellow is taken upt by one cardiac cell only or by a small integral number of cellular units to the exclusion of adjacent cells. It is concluded that the permeability of the discs of an injured cardiac cell decreases during healing over.


Low resistance pathways between myocardial cells.

To test the hypothesis of whether the intercalated discs represent a low resistance to diffusing ions, a method was developed to study the longitudinal diffusion of radioactive potassium (42K), tetraethylammonium ([14C]TEA), and the fluorescent dye Procion yellow (PY) in sheep and calf heart bundles. The method involved 1) loading the cells, 2) allowing the ions to diffuse for periods of 2-6 hr, 3) freezing the bundle in liquid air and cutting it into equal slices of 0.5 mm, 4) measuring the concentration of the ion in each slice. From the results, the diffusion of coefficients were considered to be due partially to the discs and partially to the myoplasm. The permeabilities of the nexal membranes were 7.68-10(-3), 1.27-10(-3), and 1.4-10(-6) cm/sec for 42K, 14C-TEA, and PY. These values are 9,600, 21,000, and 220 times more than the corresponding ones for the surface membrane. The disc resistance for potassium, the main intracellular charge carrier, was about 0.9 ohm cm2. From the van der Waals sizes of the ions, the diameter of the nexal pores has to be 10-15 A. It is concluded that the junctions between myocardial cells have low resistances and that propagation of action potentials is possible by local circuit currents.


Composition of cardiac muscle troponin.

Preparations of troponin from cardiac muscle consist of functionally the same subunits as skeletal troponin, that is TN-T, TN-I, and TN-C. Cardiac TN-T and TN-I have, however, higher molecular weights than those of skeletal muscle. Only TN-C from both sources does not differ in respect to the molecular weight, isoelectric point, and ability to bind calcium or strontium.


Inhibition of calcium-dependent action potentials in mammalian myocardium by specific inhibitors of the transmembrane calcium conductivity (verapamil, D 600).

Cat papillary muscles were depolarized from about -80 mV to -50 mV by addition of KCl to Tyrode's solution. This causes an inactivation of the Na-carrying system so that the remaining transmembrane inward current is due, in practice, to Ca. Such action potentials show a reduced rate of rise, a greater overshoot, and a shorter duration. These parameters vary somewhat with the strength of stimulation and, particularly, with frequency. Excitability as well as contractility of the K-depolarized fibers are completely abolished by Ca withdrawal or by addition of verapamil or D 600, which block the transmembrane Ca inward current specifically. Conversely, extra Ca or epinephrine overcomes the verapamil and C 600 effects by increasing the transmembrane Ca influx. As soon as the papillary muscles are returned to Tyrode's solution with normal K0 the Na-carrying system is reactivated. Then Ca withdrawal or Ca-antagonistic compounds lose their inhibitory influence on excitation, whereas excitation-contraction uncoupling persists.


The role of myocardial membrane leakage channels in the production of fibrillation: studies with an analog computer model.

The conditions under which automatic activity and fibrillation can occur were studied through the use of an analog model. Parameters (transmembrane active and passive properties) were established from biological data of mammalian myocardial fibers. The definition of instability of membrane potential can be given by the following functions of inward and outward steady state current (I) to voltage relationships of the membrane. 1) With decreasing angle between the tangent of the slope of the Iout and (-1) Iin, instability increases at constant potential. 2) Instability is also a function of the membrane potential as related to peak inward current (nonsteady state) at a given angle. 3) Maximum peak inward current and minimum angle produced such instability as to cause fibrillation. The most likely explanation is that automaticity and/or fibrillation is induced by leakage currents which change the normal current/voltage relatiosnhip in the described manner. The membrane leakage currents could be specific to sodium or unspecific.


The ionic basis of membrane excitation in ordinary myocardial fibers: some aspects of the sodium and calcium conductance.

Ionic currents in heart muscle are usually described in terms of the Hodgkin-Huxley theory for nerve fibers. Attention is paid to some aspects of the sodium and calcium conductance which seem to be specific for heart muscle: 1) recent findings indicate that repriming of the sodium and calcium conductance in heart muscle cannot be described as the reverse process of inactivation; 2) the existence of an important calcium current is well established, but controversial findings have been obtained for the time constant of inactivation; 3) Na and Ca interact in determining the slow channel current. Depending on the external Na and Ca concentration, antagonistic as well as synergistic effects may be obtained. An explanation is offered for these contradictory results.


The mechanism of supraventricular tachycardia induced by a single premature beat in the isolated left atrium of the rabbit. I. Circus movement as a consequence of unidirectional block of the premature impulse.

In the isolated left atrium of the rabbit tachycardia could be elicited by a single stimulus shortly after the refractory period. The activation pattern of the preparation was mapped by means of multiple extracellular recordings. It could be demonstrated that a circus movement of the activation in a relatively small part of the atrial myocardium was responsible for the tachycardia. This phenomenon was studied on a cellular level with multiple microelectrode recordings. The impulse of the premature beat, when followed by a tachycardia, was one way only, while in the other directions the conduction failed completely or occurred with such decrement that the impulse died out. These differences in conductivity were connected with spatial differences in the refractory period. Therefore the excitability of the fibers surrounding the stimulating electrod was not restored to the same level at the moment the premature beat was elicited. Spatial dispersion in the refractory period was important for the occurrence of unidirectional block and thus for the initiation of circus movement and tachycardia.


The mechanism of supraventricular tachycardia induced by a single premature beat in the isolated left atrium of the rabbit. II. The termination of the tachycardia.

Tachycardias induced by a single stimulus in the left atrium of the rabbit, are based on a circus movement of the impulse through the atrial myocardium. Circus movement often stopped spontaneously after only one beat ("coupled extrasystole") or after a small number of beats. This frequent early cessation of circus movement is explained by the relatively high conduction velocity and relatively long refractory period in the early stage of tachycardia. As an exception tachycardia lasted for a longer period. The circulating impulse then could always be interrupted by the application of a properly timed stimulus. In this case the circulating impulse will encounter the activation wave elicited by the stimulus. This resulted either in termination or resetting of the tachycardia.


Role of sympathetic excitation in generating arrhythmias in early and late phases of ectopic responses after coronary arterial occlusion in dog heart.

The three phases of arrhythmias that develop within specific durations of occlusion of a coronary artery of the dog have been reviewed and characterized. The intravenous administration of practolol as described has virtually prevented the occurrence of arrhythmic activity during the first 7-8 hr after occlusion and kept the frequency at a much reduced level as compared with controls through 10 or 11 hr, but not appreciably longer. This means that first and second phase arrhythmias were almost abolished, and development of third phase ventricular tachycardia was significantly retarded, but not prevented. It is concluded that sympathetic stimulation is an important component in the effective excitation of ectopic activity during the first and second phases, but contributed no more than a minor component to the fully developed third phase activity.


Early ventricular fibrillation in the baboon: possible role of epicardial ST segment changes.

The changes in epicardial ST segment and the severity of the infarct defined by the onset of primary ventricular fibrillation were monitored in baboons after ligation of the anterior descending coronary artery. Although an increase in the ratio of the total ST segment elevation over the maximal drop of isoelectric baseline appeared to precede the onset of ventricular fibrillation, further data is needed for establishing a clear relation between these parameters.


Relationship between myocardial metabolism and epicardial ST segment alterations during myocardial ischemia.

Acute myocardical ischemia was produced by ligating the midlevel left anterior descending coronary artery for 17 min in anesthetized dogs. Epicardial electrocardiograms were recorded from 15 sites surrounding the area of left anterior descending coronary artery ligation with a smooth tip, rounded epicardial electrode. Sites of ST segment elevation and isoelectric sites within the grossly ischemic portion of the left ventricle were needle biopsied to obtain tissue samples of less than 6 mg wet weight to assess myocardial metabolism at these precise sites. Epicardial areas of ST segment elevation had marked lactate accumulation and high energy phosphate depletion. Isoelectric sites were areas of either no lactate accumulation or mild lactate accumulation and high energy phosphate concentrations that were greater than those found at site of ST segment elevation. Thus, the data obtained indicate that epicardial sites of ST segment elevation are locations of profound anaerobic metabolism and of both epicardial and endocardial ischemia.


Calcium-dependent depolarizations and contractions in ventricular myocardial fibers: effects of adrenaline and cardiac glycosides.

Intracellular membrane potentials and contractions were recorded in ventricular trabeculae from sheep and calf hearts. Using a sucrose gap and constant current pulses of 500 msec duration, Ca-dependent depolarizations were elicited in Ca-containing Tyrode's solution + tetrodotoxin (TTX) (1-2 X 10(-5) gm/ml; [Na]e 149.2 mM) or in Na-free solution with sucrose as sodium substitute. Adrenaline (10(-8) -5 X 10(-7) gm/ml), which has been shown to enhance Ca inward current, increased (dV/dt)max and contractile force both in Na-free and in Na-containing solutions + TTX. Digitoxigenin (10(-7) -3 X 10(-7) gm/ml), however, did not change (dV/dt)max and contractions in the absence of Na. In the presence of Na (+TTX), digitoxigenin increased contractile force but decreased (dV/dt)max. Under the assumption that the Ca-dependent depolarizations are carried by Ca it is concluded 1) that in contrast to adrenaline, digitoxigenin does not increase the permeability of the myocardial cell membrane to Ca and 2) that the positive inotropic effect of digitoxigenin is not due to an enhancement in Ca inward current during depolarization.


Influence of glycosides on myocardial potassium and sodium concentration in acute and chronic potassium deficiency.

The analytical assay of intracellular potassium ([Ki]) and sodium ([Nai]) concentration of guinea pig papillary muscle measured in in vitro experiments shows that: 1) 5 X 10(-7) M g-strophanthin causes a decrease of [Ki] under control conditions, in acute as well as in chronic potassium deficiency, 2) a more marked glycoside effect is seen when the extracellular potassium concentration is reduced from 4.7 to 2mEq/1; this finding, therefore, is in good agreement with the observation that glucoside binding to its receptor at the cellular membrane is enhanced when potassium concentration is decreased, 3) whereas in chronic potassium deficiency normal [Ki] and [Nai] are maintained, acute potassium deficiency is accompanied by a loss of cellular K and gain of cellular Na. Under the influence of cardioactive glycosides, in chronic potassium depletion higher intracellular potassium and lower intracellular sodium concentrations are maintained than in acute potassium depletion. It is supposed tha t the net changes which are caused by a reduction of [Ke] in acute potassium deficiency in contrast to chronical potassium deficiency predispose to glycoside toxicity. These changes may therefore be the cause of the clinical observation that acute hypokalemia is associated with a greater glycoside sensitivity than chronic potassium deficiency.


Altered tissue digoxin uptake after a toxic dose.

Tissue distribution and left ventricular (LV) effects of digoxin were studied after intravenous administration of low and high doses to dogs. LV dP/dt was increased by 0.03 mg/kg digoxin in nine, group A, and digoxin-induced arrhythmias or death occurred after 0.14 mg/kg in nine others, group B. Two hours after dosing during the slow excretion phase confirmed by serial serum sampling, the animals were killed. Serum and tissue extract digoxin determinations were performed by radioimmunoassay. Digoxin levels in group A were serum 3.9 ng/ml, kidney 428 ng/gm wet wt, liver 41, pancreas 39, diaphragn 21, apex, freewall, and septum LV 117-122, right ventricle (RV) 105, left atrium (LA) 51, right atrium (RA) 50, and the serum to apex LV ration was 1:32. The tissue contents and distribution were similar to previous [3H]digoxin data. The concentrations were higher in B; for all p less than 0.001. The toxic to therapeutic concentration ratios were serum 10, kidney 2.8, liver 5.5. pancreas 5,4, diaphragm 6.5, LV 4.3, RV 4.0, LA 3.5, RA 3.4. The serum to LV ratio was lower at 1:13, p less than 0.001. Myocardial toxicity was associated with marked but apparently limited increases in tissue digoxin content in this preparation. The disproportionately high serum level suggests paralysis or saturation of kidney and other tissue binding resulting in lower serum to tissue concentration ratios. Whenever serum to tissue ratios vary from expected values, serum digoxin levels may not be linearly related to tissue content or cardiac effects.


Reversible and irreversible forms of contractile failure caused by disturbances by general anesthetics in myocardial ATP utilization.

Overdoses of several volatile anesthetics (ether, chloroform, ethyl chloride, halothane, methoxyflurane) as well as of various barbiturates lead to severe contractile failure of the heart. In all cases it was found that at the stage of maximal failure the myocardial stores of ATP and phosphocreatine were increased, indicative of reduced high energy phosphate utilization. Barbiturate-induced failure can be fully reversed by the intravenous injection of CaCl2, isoproterenol, or strophanthin. Simultaneously ATP and phosphocreatine concentrations become normal. In contrast, cardiac failure caused by volatile anesthetics proved to be resistant to this therapy. Electron micrographs showed a normal structure of the transverse tubules in the case of barbiturate failure. On the other hand, after the application of volatile anesthetics, a striking dilatation of the transverse tubular system was observed. The irreversibility of this latter type of contractile failure is probably caused by permanent damage of myocardial ultrastructures involved in excitation-contraction coupling.


On the mechanism of the negative inotropic action of halothane and propanidide.

1) Halothane and propanidide reduce the contractile force of guinea pig isolated atria in a concentration-dependent manner. The approximate concentrations required to bring about a half-maximal pharmacological effect are within the same order of magnitude as the concentrations found in whole blood during general anesthesia of guinea pigs. 2) It seems most likely that the initial effect of halothane or propanidide occurs at the cell membrane. 3) Halothane and propanidide accelerate and enhance the uptake of calcium ions by the cell membrane, so that less ionized calcium will be available for excitation contraction coupling. This phenomenon readily explains the negative inotropic action of both drugs and confirms the presumption that the cell membrane is the initial site of pharmacological attack.


Outward current and electrogenic sodium pump in Purkinje fibers.

The effects of metabolic inhibitors (ouabain, dihydroouabain, and 2,4-dinitrophenol (2,4-DNP) and of cooling on the membrane current of Purkinje fibers were studied by means of a voltage clamp. Within seconds after cooling or application of the drugs the outward current was found to be reduced. On longer cooling or poisoning, the potassium equilibrium potential was shifted in positive direction, the time-dependent membrane currents were depressed, and possibly the potassium conductance was altered. It is suggested that the early reduction in outward current is caused by inhibition of an electrogenic sodium pump.


Myocardial oxygen consumption in isometric contraction of various strengths due to paired stimulation and quick-release.

In all of the experiments described, the oxygen consumption during isometric contraction was dependent solely upon the magnitude of active tension developed, and not on the rate of tension development or on the duration of contraction. There is a constant linear relationship between tension development and oxygen uptake. Any sudden interruption of active tension in the rising phase of the contraction terminates the energy utilization by the contractile system. These findings provide evidence to suggest that in isometric contraction of heart muscle, a rigid and constant coupling exists in the transformation of chemical energy to the mechanical tension.


Multiple measurement of intranural myocardial oxygen tension.

A method was developed for measuring the intramural oxygen tension in the ventricular wall (MpO2). The 10 electrodes of intramural needles are employed simultaneously for measurement of MpO2, and, by means of the same amplifiers and registration system, of the electrogram. In this way information could be obtained about the local MpO2 and the local electrical activity obtained from over 100 points in the ventricular wall. In the normal in situ dog heart we found an MpO2 of 5-90 mm Hg (mean 32 mm Hg). When the arterial pO2 was raised, the mean value of MpO2 was decreased. Directly after the start of a period of severe hypoxia a marked fall in MpO2 could be observed, which was reversible after return to the normoxic situation, provided that the hypoxic period was short. Changes in heart rate had only transient effects on the MpO2. Heart massage of the fibrillating heart in the open-chested dog was effective in restoring the arterial pO2, but gave no significant rise in MpO2 which did not exceed 5 mm Hg.


Myocardial wall thickness as a measurement of left ventricular ischemia.

Using a newly developed myocardial wall thickness gauge, the change in the left ventricular wall thickness was measured during a period of partial myocardial ischemia and compared with changes and other parameters of left ventricular function. This study revealed that major changes of systolic wall thickness occur without any significant change in left ventricular function parameters.